Structural insight into filament formation by mammalian septins
Abstract
Septins are GTP-binding proteins that assemble into homo- and hetero-oligomers and filaments. Although they have key roles in various cellular processes, little is known concerning the structure of septin subunits or the organization and polarity of septin complexes. Here we present the structures of the human SEPT2 G domain and the heterotrimeric human SEPT2-SEPT6-SEPT7 complex. The structures reveal a universal bipolar polymer building block, composed of an extended G domain, which forms oligomers and filaments by conserved interactions between adjacent nucleotide-binding sites and/or the amino- and carboxy-terminal extensions. Unexpectedly, X-ray crystallography and electron microscopy showed that the predicted coiled coils are not involved in or required for complex and/or filament formation. The asymmetrical heterotrimers associate head-to-head to form a hexameric unit that is nonpolarized along the filament axis but is rotationally asymmetrical. The architecture of septin filaments differs fundamentally from that of other cytoskeletal structures.
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The mitotic Septin complex consisting of Septin 2, 6 and 7 has a calculated dipole moment of 2711 Debyes (D).
“The mitotic Septin complex consisting of Septin 2, 6 and 7, possesses a high calculated dipole moment of 2711 Debyes (D)”
From Tumor Treating Fields Perturb the Localization of Septins and Cause Aberrant Mitotic Exit (2015) · cites this paper as [50]
The dipole vectors of the constituent heterotrimeric subunits are predicted to be in roughly the same plane and direction in each bound subunit in the hexamer.
“Interestingly, the orientation of the dipole vectors of the constituent heterotrimeric subunits is predicted to be in roughly the same plane and direction in each bound subunit in the hexamer.”
From Tumor Treating Fields Perturb the Localization of Septins and Cause Aberrant Mitotic Exit (2015) · cites this paper as [50]
The Septin heterotrimer oligomerizes to form larger hexamers.
“Further, these heterotrimers further oligomerize to form larger hexamers [50].”
From Tumor Treating Fields Perturb the Localization of Septins and Cause Aberrant Mitotic Exit (2015) · cites this paper as [50]
The orientation of the dipole vectors of the two constituent heterotrimers is predicted to be roughly parallel to each other in the same orientation within the resulting hexamer.
“Significantly, the orientation of the dipole vectors of the two constituent heterotrimers is predicted to be roughly parallel to each other in the same orientation within the resulting hexamer [50].”
From Tumor Treating Fields Perturb the Localization of Septins and Cause Aberrant Mitotic Exit (2015) · cites this paper as [50]
Septins form short filaments that self-assemble into parallel arrays which are non-polar in nature.
“Septins form short filaments that self-assemble into parallel arrays which are non-polar in nature [50, 57, 58].”
From Tumor Treating Fields Perturb the Localization of Septins and Cause Aberrant Mitotic Exit (2015) · cites this paper as [50]
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- Authors
- Sirajuddin, M., Farkasovsky, M., Hauer, F., Kühlmann, D., Macara, I. G., Weyand, M., Stark, H., & Wittinghofer, A.
- Affiliations
- Max Planck Institute of Molecular Physiology (DE)
- Max Planck Society (DE)
- University of Virginia (US)
- Corresponding author
- Wittinghofer, Alfred
- Venue
- Nature
- Published
- 2007-07-18
- Volume
- 449
- Issue
- 7160
- Pages
- 311-315
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2078116784
- Cited by
- 481
- References
- 45
- Citations by year
- 2026: 19 · 2025: 15 · 2024: 15 · 2023: 20 · 2022: 25 · 2021: 32 · 2020: 18 · 2019: 25 · 2018: 30 · 2017: 29 · 2016: 47 · 2015: 22 · 2014: 30 · 2013: 21 · 2012: 18
- FWCI
- 10.06
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DORA PSI (Paul Scherrer Institute) (submittedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- Max Planck Digital Library (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- International Max Planck Research School for Environmental, Cellular and Molecular Microbiology
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Keywords
- septins, SEPT2, SEPT6, SEPT7, septin filaments, G-domain, heterotrimeric complex, filament assembly, coiled coil, nucleotide binding site, rotational asymmetry, cytoskeleton, G proteins, oligomerization
- MeSH terms
- Binding Sites, Cytoskeletal Proteins, Humans, Models, Molecular, Nucleotides, Phosphoric Monoester Hydrolases, Protein Structure, Tertiary, Crystallography, X-Ray, Cell Cycle Proteins, GTP-Binding Proteins, Dimerization, Protein Structure, Quaternary, Multiprotein Complexes, Septins
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