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Cited by 686Protein Structure and DynamicsEnzyme Structure and FunctionBiochemical and Structural Characterization

3D domain swapping: As domains continue to swap

Open access
Liu, Yanshun, Eisenberg, David·2002·Protein Science
DOI 10.1110/ps.0201402PMC PMC2373619
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Abstract

Three‐dimensional (3D) domain swapping creates a bond between two or more protein molecules as they exchange their identical domains. Since the term '3D domain swapping' was first used to describe the dimeric structure of diphtheria toxin, the database of domain‐swapped proteins has greatly expanded. Analyses of the now about 40 structurally characterized cases of domain‐swapped proteins reveal that most swapped domains are at either the N or C terminus and that the swapped domains are diverse in their primary and secondary structures. In addition to tabulating domain‐swapped proteins, we describe in detail several examples of 3D domain swapping which show the swapping of more than one domain in a protein, the structural evidence for 3D domain swapping in amyloid proteins, and the flexibility of hinge loops. We also discuss the physiological relevance of 3D domain swapping and a possible mechanism for 3D domain swapping. The present state of knowledge leads us to suggest that 3D domain swapping can occur under appropriate conditions in any protein with an unconstrained terminus. As domains continue to swap, this review attempts not only a summary of the known domain‐swapped proteins, but also a framework for understanding future findings of 3D domain swapping.

AI snapshot

Written from the paper’s full text.

TL;DR

This review summarizes about 40 structurally characterized 3D domain-swapped proteins, emphasizing diverse swapped domains, flexible hinge loops, and examples including RNase A, T7 helicase, human prion, and cystatin C. It proposes that 3D domain swapping can occur under appropriate conditions in any protein with an unconstrained terminus and may relate to oligomerization, allostery, and amyloid formation.

Key findings

  • About 40 domain-swapped proteins have known structures; all swapped domains except one are from either the N or C terminus, and swapped domains vary widely in size, sequence, and secondary structure, with no specific sequence motif found.
  • RNase A can swap both N- and C-terminal domains: structures include the N-terminal swapped dimer (2.1 Å), C-terminal swapped dimer (1.75 Å), and cyclic C-terminal swapped trimer (2.2 Å); RNase A is the first protein found to form both linear and cyclic domain-swapped oligomers.
  • Blood coagulant factor IX/X-binding protein is the only known example of 3D domain swapping in the middle of the molecule and the only known domain-swapped heterodimer; T7 gene 4 ring helicase forms open oligomeric domain swapping along a six-fold screw axis and requires swapping for hexamerization and activity.
  • Human prion and human cystatin C form domain-swapped dimers and are amyloidogenic, suggesting domain swapping and amyloid formation may share common intermediates; physiological relevance is supported for some proteins, such as RNase A dimerization at pH 6.5 and 37°C with a dissociation constant of ∼2 mM, but considered artifact for others such as barnase at pH 4.5 and truncated TrkA Domain 5.

Methods

  • Review and structural synthesis of domain-swapped proteins, tabulating bona fide examples, quasi-domain-swapped proteins, and candidates in Tables 1–3 with PDB codes, residue counts, swapped domains, hinge loops, and functions.
  • Compares crystal and NMR structures plus biochemical data from cited studies, with detailed discussion of six examples: IX/X-binding protein, RNase A trimers, glyoxalase I, T7 helicase, human prion, and human cystatin C.
  • Main analysis is qualitative structural comparison and synthesis of a free-energy/mechanism model for 3D domain swapping.

Limitations

  • The paper states that the mechanism of 3D domain swapping remains elusive, few studies have examined it, and it is unclear whether the domain-swapped dimer is the building block for amyloid fibers.
  • The paper states that RNase A tetramer structures are unknown and models are hypothetical; glyoxalase I C-terminal domain swapping is ambiguous because there are two ways to define the monomer, and the crystal structure of the monomer is needed.
  • Evident from the text: this is a review without new experimental data, and some hinge-loop residues in candidate proteins are speculative and marked with question marks.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1110/ps.0201402

Cites

107 of 107 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 83 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Most swapped domains in domain-swapped proteins are at either the N or C terminus.

    “Analyses of the now about 40 structurally characterized cases of domain-swapped proteins reveal that most swapped domains are at either the N or C terminus”
    • Also stated in: § Advances in 3D domain swapping · plain
      “One common feature of these domain-swapped proteins is that all the swapped domains (except in one protein) are from either the N terminus or the C terminus.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The set of about 40 structurally characterized domain-swapped proteins is representative of domain-swapped proteins generally.
  • Findingown data

    The swapped domains of domain-swapped proteins are diverse in their primary and secondary structures.

    “the swapped domains are diverse in their primary and secondary structures”
    • Also stated in: § Diversity of the swapped domains · plain
      “The swapped domains have diverse sizes and sequences.”
    • Also stated in: § Diversity of the swapped domains · plain
      “The swapped domains also have diverse secondary struc-tures.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The set of about 40 structurally characterized domain-swapped proteins is representative of domain-swapped proteins generally.
  • Findingcitation

    Several recent structural studies support the flexibility of hinge loops.

    “Several recent structural studies of 3D domain swapping further support the flexibility of the hinge loops.”
    Quote in the paperNot a substantial claim
  • Findingnone given

    When the hinge loop forms a β-strand or an α-helix, the oligomeric form is favored over the monomer.

    “A common feature is that when the hinge loop forms a ␤-strand or an ␣-helix, the oligomeric form is favored over the monomer.”
    Quote in the paperSubstantial claim
  • Findingcitation

    The only exception found to date to the rule that most swapped domains are at either the N or C terminus is blood coagulant factors IX/X-binding protein (IX/X-bp).

    “The only exception found to date is blood coagulant factors IX/X-binding protein (IX/X-bp, Mizuno et al. 1997).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Mizuno et al. 1997

      Not checked in the free run.

  • Classified as probably not a substantial claim. 3
  • May combine two claims. 46

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingnone given

    About 40 domain-swapped proteins have known structures.

    “To date, about 40 domain-swapped proteins have known structures.”
    • Also stated in: § New examples of 3D domain swapping in proteins · plain
      “To date, about 40 domain-swapped proteins have been reported.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The set of about 40 structurally characterized domain-swapped proteins is representative of domain-swapped proteins generally.

  • May combine two claims.

    Findingnone given

    IX/X-bp is the only known example of a domain-swapped heterodimer; all other domain-swapped proteins are homooligomers.

    “In addition, IX/X-bp is the only known example of a domain-swapped heterodimer; all other domain-swapped proteins are homooligomers.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The set of about 40 structurally characterized domain-swapped proteins is representative of domain-swapped proteins generally.

  • May combine two claims.

    Premisecitation

    In the less abundant RNase A dimer, the N-terminal helix is swapped; in the other dimer, the C-terminal strand is swapped.

    “Structures of both dimers (Fig. 2) reveal that the N-terminal helix is swapped in the less abundant dimer (the N-terminal swapped dimer, previously named the minor dimer) (Liu et al. 1998), whereas the Cterminal strand is swapped in the other dimer (the C-terminal swapped dimer, previously named the major dimer) (Liu et al. 2001).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Liu et al. 1998

      Not checked in the free run.

    • cites Liu et al. 2001

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    RNase A forms two types of dimers, with one dimer more abundant than the other.

    “Further studies showed that there are two types of dimers of RNase A, formed with one dimer more abundant than the other dimer (Libonati et al. 1996;Gotte et al. 1999).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Libonati et al. 1996

      Not checked in the free run.

    • cites Gotte et al. 1999

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    3D domain swapping does not depend on the protein sequence or secondary structure.

    “In summary, the diversity of the swapped domains indicates that 3D domain swapping does not depend on the protein sequence or secondary structure.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    3D domain swapping is required for the hexamerization and the activity of T7 helicase.

    “Therefore, 3D domain swapping is required for the hexamerization and the activity of T7 helicase.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    The dissociation constant for the RNase A dimer at pH 6.5 and 37°C is about 2 mM, about 20-fold greater than the concentration of RNase A in the bovine pancreas.

    “The dissociation constant for the dimer at this condition is ∼2 mM, which is about 20-fold greater than the concentration of RNase A in the bovine pancreas”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Park and Raines 2000

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    3D domain swapping in RNase A exists in vivo and may play some physiological role.

    “These results suggest that 3D domain swapping in RNase A exists in vivo and may play some physiological role.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationnone given

    By examining domain-swapped proteins, domain swapping is physiologically relevant in some proteins, but not in others.

    “By examining domain-swapped proteins, we conclude that domain swapping is physiologically relevant in some proteins, but not in others.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationcitation

    T7 helicase provides structural evidence for 3D domain swapping in a hexamer, supporting the proposal that 3D domain swapping is a mechanism for extended protein oligomerization.

    “T7 helicase provides the structural evidence for 3D domain swapping in a hexamer, supporting the proposal that 3D domain swapping is a mechanism for extended protein oligomerization (Bennett et al. 1995).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Bennett et al. 1995

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    These studies show that domain swapping and amyloid formation may share common intermediates, and thus suggest that 3D domain swapping is a possible mechanism for amyloid formation.

    “Although it is unclear whether the domain-swapped dimer is the building block for these fibers, these studies show that domain swapping and amyloid formation may share common intermediates, and thus suggest that 3D domain swapping is a possible mechanism for amyloid formation.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    3D domain swapping does not require or prefer certain types of secondary structure.

    “This diversity shows that 3D domain swapping does not require or prefer certain types of secondary structure.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    In the less abundant RNase A trimer, only the C-terminal strand is swapped, and the structure is cyclic.

    “In the less abundant trimer, only the C-terminal strand is swapped, and the structure is cyclic (cyclic C-terminal swapped trimer, previously named the minor trimer, Fig. 2) (Liu et al. 2002).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Liu et al. 2002

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S1 (asserted), S3 (load-bearing), S4 (based). May combine two claims.

    Interpretationnone given

    The 'cab'-type β class carbonic anhydrase, RecA, and the T7 helicase display open-oligomeric 3D domain swapping, which can be seen in crystals because the oligomer screw-axis symmetry is also a symmetry of the crystal.

    “In summary, the”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    RNase A oligomers display two basic types of 3D domain swapping, and with two types of swapping, a protein can form a variety of oligomers.

    “Thus, RNase A oligomers display two basic types of 3D domain swapping, and show that with two types of swapping, a protein can form a variety of oligomers.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Further biochemical studies support the trimeric model and indicate that it belongs to the more abundant RNase A trimer.

    “Further biochemical studies support this model and indicate that the model belongs to the more abundant trimer (linear N-and C-terminal swapped trimer, previously named the major trimer).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Liu et al. 2002

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    3D domain swapping in BS-RNase is necessary for its immunosuppression activity and allostery activity.

    “3D domain swapping in bovine seminal ribonuclease (BS-RNase, sharing 80% sequence identity with RNase A, Mazzarella et al. 1993) was reported to be necessary for its immunosuppression activity and allostery activity (Piccoli et al. 1988;Cafaro et al. 1995)”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Piccoli et al. 1988

      Not checked in the free run.

    • cites Cafaro et al. 1995

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Cyanovirin-N was crystallized under low pH and shown to be domain-swapped.

    “Cyanovirin-N (Yang et al. 1999) was also crystallized under low pH and was shown to be domain-swapped.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Yang et al. 1999

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    BS-RNase, T7 helicase, cro repressor, phosphoenolpyruvate mutase, T4 endonuclease VII, IX/X-binding protein, and bleomycin resistance protein exist as domain-swapped oligomers in vivo.

    “These proteins include BS-RNase (Mazzarella et al. 1993), T7 helicase (Singleton et al. 2000), cro repressor (Anderson et al. 1981), phosphoenolpyruvate mutase (Huang et al. 1999), T4 endonuclease VII (Raaijmakers et al. 1999), IX/X-binding protein (Mizuno et al. 1997), and bleomycin resistance protein (Dumas et al. 1994).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Mazzarella et al. 1993

      Not checked in the free run.

    • cites Singleton et al. 2000

      Not checked in the free run.

    • cites Anderson et al. 1981

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    3D domain swapping is a mechanism for allostery and signal sensing in a macromolecule, and therefore for regulating biological functions of proteins.

    “These studies provide evidence for 3D domain swapping as a mechanism for allostery and signal sensing in a macromolecule, and therefore for regulating biological functions of proteins.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Mutations that shift the equilibrium are distant from the hinge loop, suggesting that the strain at the hinge loop can be sensed by remote mutation sites.

    “The mutations that shift the equilibrium are distant from the hinge loop, suggesting that the strain at the hinge loop can be “sensed” by the remote mutation sites.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    3D domain swapping regulated by ligands was reported in glyoxalase I and p13suc1, where the equilibrium between monomer and dimer is regulated by glutathione and phosphopeptide, respectively.

    “3D domain swapping regulated by ligands was reported in glyoxalase I (Saint-Jean et al. 1998) and p13suc1 (Schymkowitz et al. 2001), where the equilibrium between the monomer and the dimer is regulated by glutathione and phosphopeptide, respectively”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Saint-Jean et al. 1998

      Not checked in the free run.

    • cites Schymkowitz et al. 2001

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Macromolecular crowding increases protein local concentration and facilitates protein oligomerization.

    “Macromolecular crowding increases protein local concentration and facilitates protein oligomerization (Cole and Ralston 1994;Lindner and Ralston 1995;Rivas et al. 1999).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Cole and Ralston 1994

      Not checked in the free run.

    • cites Lindner and Ralston 1995

      Not checked in the free run.

    • cites Rivas et al. 1999

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Several domain-swapped oligomers are obtained under nonphysiological low pH, and the biological functions of the oligomers are unknown.

    “Several domain-swapped oligomers are obtained under nonphysiological low pH, and the biological functions of the oligomers are unknown.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    Smaller domains form domain-swapped oligomers more easily than larger domains, and may do so under nonphysiological conditions.

    “these examples suggest that smaller domains form domain-swapped oligomers more easily than larger domains, and may do so under nonphysiological conditions.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    The active forms of these proteins are domain-swapped, suggesting that their 3D domain swapping is related to their biological functions in vivo.

    “However, the active forms of these proteins are domain-swapped, suggesting that their 3D domain swapping is related to their biological functions in vivo.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Macromolecular crowding in cells increases the population of domain-swapped oligomers and adds support to the possible physiological relevance of 3D domain swapping.

    “Thus, macromolecular crowding in cells increases the population of domain-swapped oligomers and thus in a general way adds support to the possible physiological relevance to 3D domain swapping.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationcitation

    Domain swapping in Domain 5 is regarded as a consequence of truncation of the whole protein and is not of physiological significance.

    “Therefore, domain swapping in Domain 5 is regarded as a consequence of the truncation of the whole protein (Ultsch et al. 1999) and is not of physiological significance.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Ultsch et al. 1999

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The T4 endonuclease VII dimer (PDB 1EN7; 157 residues per subunit) is a candidate for 3D domain swapping, with 60 residues in the swapped domain and hinge loop residues 63-72.

    “| T4 endonuclease VII dimer (Raaijmakers | 1EN7 | 157 | 60 | 63-72 (?) | Mismatch repair, Resolving | N-terminal helix |”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Raaijmakers et al. 1999

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The dimer of one repeat of α-spectrin (PDB 2SPC; 107 residues per subunit) is a candidate for 3D domain swapping, with 32 residues in the swapped domain and hinge loop residues 72-75.

    “| Dimer of one repeat of ␣-spectrin | 2SPC | 107 | 32 | 72-75 | Cytoskeletal protein | C-terminal ␣-helix |”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Yan et al. 1993

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The designed coiled coil dimer (PDB 1G6U; 48 residues per subunit) is a candidate for 3D domain swapping, with 14 residues in the swapped domain and hinge loop residues 33-34.

    “| Designed coiled coil dimer (Ogihara | 1G6U | 48 | 14 | 33-34 (?) | Unknown | C-terminal ␣-helix |”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Ogihara et al. 2001

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The Cab-type β class carbonic anhydrase (PDB 1G5C; 170 residues per subunit) is a candidate for 3D domain swapping, with 12 residues in the swapped domain and hinge loop residues 13-23.

    “| Cab-type ␤ class carbonic anhydrase | 1G5C | 170 | 12 | 13-23 (?) | Catalyzing reversible hydration | N-terminal ␣-helix |”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Strop et al. 2001

      Not checked in the free run.

  • May combine two claims.

    Interpretationnone given

    In several proteins, 3D domain swapping is found in the active form, whereas in other proteins, domain swapping seems an artifact of truncation of the whole molecules.

    “In several proteins, 3D domain swapping is found in the active form of these proteins, whereas in other proteins, domain swapping seems an artifact of truncation of the whole molecules.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    The CesT dimer (PDB 1K3E; 156 residues per subunit) is a candidate for 3D domain swapping, with 32 residues in the swapped domain and hinge loop residues 33-36.

    “| CesT dimer (Luo et al. 2001) | 1K3E | 156 | 32 | 33-36 | Molecular chaperone in type | N-terminal ␣-helix |”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Luo et al. 2001

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The dUTPase trimer (PDB 1DUD; 136 residues per subunit) is a candidate for 3D domain swapping, with 10 residues in the swapped domain and hinge loop residues 125-126.

    “| dUTPase trimer (Larsson et al. 1996) | 1DUD | 136 | 10 | 125-126 (?) dUTP hydrolysis | C-terminal strand |”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Larsson et al. 1996

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The citrate synthase dimer from chicken heart (PDB 1CTS; 433 residues per subunit) is a candidate for 3D domain swapping, with 10 residues in the swapped domain and hinge loop residues 417-423.

    “| Citrate synthase dimer from chicken heart | 1CTS | 433 | 10 | 417-423 (?) Citrate synthesis | C-terminal helix |”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Remington et al. 1982

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The heat shock protein 33 dimer (PDB 1HW7; 255 residues per subunit) is a candidate for 3D domain swapping, with 75 residues in the swapped domain and hinge loop residues 178-184.

    “| Heat shock protein 33 dimer | 1HW7 | 255 | 75 | 178-184 (?) Molecular chaperone | C-terminal helices |”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Vijayalakshmi et al. 2001

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The bleomycin resistance protein dimer (PDB 1BYL; 122 residues per subunit) is a candidate for 3D domain swapping, with 8 residues in the swapped domain and hinge loop residues 9-11.

    “| Bleomycin resistance protein dimer | 1BYL | 122 | 8 | 9-11 (?) | Bleomycin resistance | N-terminal ␤-strand |”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Dumas et al. 1994

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  • May combine two claims.

    Premisecitation

    The Grb2-SH2 domain dimer (PDB 1FYR; 93 residues per subunit) is a candidate for 3D domain swapping, with 27 residues in the swapped domain and hinge loop residues 121-123.

    “| Grb2-SH2 domain dimer (Schiering | 1FYR | 93 | 27 | 121-123 | Binding phosphorylated | C-terminal ␣-helix |”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Schiering et al. 2000

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  • May combine two claims.

    Premisecitation

    The BTB domain of PLZF (PDB 1BUO; 120 residues per subunit) is a candidate for 3D domain swapping, with 12 residues in the swapped domain and hinge loop residues 13-23.

    “| BTB domain of PLZF (Ahmad et al. | 1BUO | 120 | 12 | 13-23 (?) | Evolutionarily conserved | N-terminal ␤-strand |”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Ahmad et al. 1998

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The phosphoenolpyruvate mutase dimer (PDB 1PGM; 295 residues per subunit) is a candidate for 3D domain swapping, with 35 residues in the swapped domain and hinge loop residues 240-260.

    “| Phosphoenolpyruvate mutase dimer | 1PGM | 295 | 35 | 240-260 (?) Converting | C-terminal helices |”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Huang et al. 1999

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The T7 gene 4-ring helicase hexamer fragment (PDB 1E0J; 326 residues per subunit) is a candidate for 3D domain swapping, with 40 residues in the swapped domain and hinge loop residues 283-305.

    “| T7 gene 4-ring helicase hexamer | 1E0J | 326 | 40 | 283-305 (?) Separation of nucleic acid | N-terminal ␣-helix |”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Singleton et al. 2000

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The SH3 domain of Eps8 (PDB 1AOJ; 65 residues per subunit) is a candidate for 3D domain swapping, with 26 residues in the swapped domain and hinge loop residues 34-39.

    “| SH3 domain of Eps8 (Kishan et al. | 1AOJ | 65 | 26 | 34-39 | Recognition of proline-rich | C-terminal |”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Kishan et al. 1997

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    The independence of 3D domain swapping from protein sequence, secondary structure and hinge loop suggests that any protein can be domain-swapped under appropriate conditions where the terminal domain of the protein is unconstrained.

    “The independence of 3D domain swapping from protein sequence, secondary structure and hinge loop suggests that any protein can be domain-swapped under appropriate conditions where the terminal domain of the protein is unconstrained.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    The beef liver catalase dimer (PDB 7CAT; 500 residues per subunit) is a candidate for 3D domain swapping, with 65 residues in the swapped domain and hinge loop residues 66-70.

    “| Catalase dimer (beef liver) (Fita and | 7CAT | 500 | 65 | 66-70 (?) | H 2 O 2 hydrolysis | N-terminal helices |”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Fita and Rossmann 1985

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The simian virus 40 oligomer (PDB 1SVA; 361 residues per subunit) is a candidate for 3D domain swapping, with 61 residues in the swapped domain and hinge loop residues 296-300.

    “| Simian virus 40 oligomer (Stehle et al. | 1SVA | 361 | 61 | 296-300 (?) Virus coat protein | C-terminal helix |”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Stehle et al. 1996

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The E. coli RecA hexamer (PDB 2REB; 352 residues per subunit) is a candidate for 3D domain swapping, with 26 residues in the swapped domain and hinge loop residues 27-39.

    “| RecA hexamer from E. coli (Story et al. | 2REB | 352 | 26 | 27-39 (?) | DNA recombination and repair | N-terminal ␣-helix |”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Story et al. 1992

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The T7 gene 4-ring helicase fragment (PDB 1CR0; 296 residues per subunit) is a candidate for 3D domain swapping, with 12 residues in the swapped domain and hinge loop residues 283-305.

    “| T7 gene 4-ring helicase fragment | 1CR0 | 296 | 12 | 283-305 (?) Unknown | N-terminal ␣-helix |”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Sawaya et al. 1999

      Not checked in the free run.

48 of 48

  • The paper relies on this without support.

    The set of about 40 structurally characterized domain-swapped proteins is representative of domain-swapped proteins generally.

    “Analyses of the now about 40 structurally characterized cases of domain-swapped proteins reveal that most swapped domains are at either the N or C terminus”
    “To date, about 40 domain-swapped proteins have known structures.”

  • The paper relies on this without support.

    The biochemical behavior of Pseudomonas putida Glx I (55% sequence identity to human Glx I) can be used to infer the active-site completeness and domain-swapping state of human Glx I.

    “Biochemical data show an equilibrium of monomer and dimer in Glx I from Pseudomonas putida (55% sequence identity to human Glx I), and both the monomer and the dimer are active (Saint-Jean et al. 1998).”
    “Based on these biochemical data, we regard human Glx I as a protein with two domains swapped, as proposed by Cameron et al. (1997).”

  • The paper relies on this without support.

    Thermodynamic activity exceeds concentration.

    “That is, thermodynamic activity exceeds concentration.”

  • The paper relies on this without support.

    The greater entropy of the monomer makes it more favored thermodynamically.

    “First, the greater entropy of the monomer makes it more favored thermodynamically.”
4 of 4

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • This target has very extensive inter-subunit interactions, including a domain swap in which part of the fold of one monomer occupies the corresponding position of a neighboring one.

    “This is an unusual target in that there are very extensive inter-subunit interactions, including a domain swap21 in which part of the fold of one monomer occupies the corresponding position of a neighboring one.”

    From Critical assessment of methods of protein structure prediction (CASP)—Round <scp>XIV</scp> (2021) · cites this paper as [21]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • C-terminal-swapped trimer is called N-terminal-swapped

    Minor

    The sentence calls the cyclic RNase A trimer N-terminal-swapped but then says it swaps C-terminal strands. Elsewhere, the paper identifies the cyclic trimer as C-terminal-swapped.

1 of 1

Cites

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Related

Authors
Liu, Y., & Eisenberg, D.
Affiliations
Howard Hughes Medical Institute (US)
Corresponding author
Eisenberg, David
ORCID
Venue
Protein Science
Publisher
Wiley
Published
2002-06
Volume
11
Issue
6
Pages
1285-1299
ISSN
  • 0961-8368 (ISSN-L)
  • 1469-896X
DOI
10.1110/ps.0201402
PMC
PMC2373619
OpenAlex
W2160082320
Cited by
684
References
106
Citations by year
2026: 6 · 2025: 15 · 2024: 16 · 2023: 14 · 2022: 12 · 2021: 37 · 2020: 21 · 2019: 21 · 2018: 18 · 2017: 18 · 2016: 41 · 2015: 31 · 2014: 34 · 2013: 25 · 2012: 35
FWCI
3.37
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor, 2460 d)
Locations
  • Protein Science (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Science Foundation
  • National Institutes of Health
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Structural Characterization
Keywords
protein-protein interaction, diphtheria toxin, amyloid proteins, protein flexibility, protein structure
MeSH terms
Animals, Humans, Models, Molecular, Protein Binding, Proteins, Protein Structure, Tertiary, Dimerization

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-10.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-10.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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