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Cited by 248HIV Research and TreatmentEnzyme Structure and FunctionHIV/AIDS drug development and treatment

X-ray crystal structures of native HIV-1 capsid protein reveal conformational variability

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Gres, Anna T., Kirby, Karen A., KewalRamani, Vineet N., Tanner, John J., Pornillos, Owen, Sarafianos, Stefan G.·2015·Science
DOI 10.1126/science.aaa5936PMC PMC4584149
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Abstract

Retroviral capsids in their native form: Capsid proteins of retroviruses form protective lattices around viral RNA molecules. The precise molecular details of how individual, full-length capsid proteins assemble to shield the viral genome; however, are not well understood. Obal et al. and Gres et al. now report high resolution crystal structures of the full length capsid proteins from Bovine Leukemia Virus and HIV-1, respectively. The two studies complement each other to reveal the dynamic nature of capsid protein assembly and of how individual capsid proteins interact in the lattice. The findings may have relevance for drug design. Science , this issue p. 95 ; see also p. 99

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  • The CA-CTDs are located beneath the hexameric ring and form dimeric inter-hexamer interactions involving mainly hydrophobic interactions between residues on helix 9 at the local twofold and residues on helix 10 at the local three-fold.

    “The CA-CTDs are located beneath the hexameric ring and form dimeric inter-hexamer interactions involving mainly hydrophobic interactions between residues on helix 9 at the local twofold [6,53] and residues on helix 10 at the local three-fold”

    From Retrovirus maturation-an extraordinary structural transformation (2016) · cites this paper as [45]

    The paper describes CA-CTD inter-hexamer contacts at the twofold interface and identifies helix H9 as part of the dimerization interface. It says earlier studies proposed hydrophobic contacts, but its native structure also reveals water-mediated hydrophilic contacts at the twofold interface; it does not establish that the interactions are mainly hydrophobic. The supplied passages are labeled Abstract and have no page number. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

  • In HIV, six CA-NTDs form a hexameric ring with a central 18 helix bundle formed by helices 1, 2, and 3, providing the main intrahexamer stability.

    “In HIV six CA-NTDs form a hexameric ring with a central 18 helix bundle formed by helices 1, 2, and 3, providing the main intrahexamer stability”

    From Retrovirus maturation-an extraordinary structural transformation (2016) · cites this paper as [45]

    The paper’s passage on capsid architecture (page not provided) describes an inner ring of six CA-NTDs held together by contacts between adjacent CA molecules. Its passage on stabilizing interactions identifies CA-NTD–CA-NTD and CA-NTD–CA-CTD contacts around the sixfold axis, but does not identify a central 18-helix bundle formed by helices 1–3 or say that bundle provides the main intrahexamer stability. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • The variable local curvatures of the hexameric CA lattice require considerable structural flexibility of the CA lattice, which has been suggested to be accommodated by the flexible linker between CA-NTD and CA-CTD, by rotations around the dimeric CA-CTD interface, and by structural changes at the trimeric CA-CTD interface.

    “This requires considerable structural flexibility of the CA lattice that has been suggested to be accommodated by the flexible linker between CA-NTD and CA-CTD [44,45 ], by rotations around the dimeric CA-CTD interface [43 ], and by structural changes at the trimeric CA-CTD interface”

    From Retrovirus maturation-an extraordinary structural transformation (2016) · cites this paper as [45]

    Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

    Experimental — accuracy not yet measured

  • While in-virus structures are currently lacking, in vitro studies indicate that the arrangement of CA in mature retroviruses is well conserved.

    “While in-virus structures are currently lacking, these in vitro studies indicate that the arrangement of CA in mature retroviruses is well conserved”

    From Retrovirus maturation-an extraordinary structural transformation (2016) · cites this paper as [45]

    The paper’s native HIV-1 CA crystal structure shows a hexagonal lattice in general agreement with earlier in vitro structures (section labeled Abstract; page unavailable). But it does not establish that CA arrangement is well conserved across mature retroviruses; its comparison with bovine leukemia virus instead emphasizes variability in CA contacts. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

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Cites

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Cited by

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Authors
Gres, A. T., Kirby, K. A., KewalRamani, V. N., Tanner, J. J., Pornillos, O., & Sarafianos, S. G.
Affiliations
  • University of Missouri (US)
  • National Cancer Institute (US)
  • University of Virginia (US)
Corresponding author
Sarafianos, Stefan G.
ORCID
Venue
Science
Publisher
American Association for the Advancement of Science (AAAS)
Published
2015-07-03
Volume
349
Issue
6243
Pages
99-103
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
DOI
10.1126/science.aaa5936
PMC
PMC4584149
OpenAlex
W1925325850
Cited by
248
References
5
Citations by year
2026: 10 · 2025: 18 · 2024: 18 · 2023: 16 · 2022: 29 · 2021: 28 · 2020: 27 · 2019: 23 · 2018: 21 · 2017: 17 · 2016: 29 · 2015: 12
FWCI
13.49
Type
journal article
Language
en
Open access
Licence
www.sciencemag.org/about/science-licenses-journal-article-reuse (vor, 366 d)
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
Funders
NIH (AI112417, AI120860, GM103368, AI076119, AI099284, AI100890, GM066087)
Topics
  • Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
  • Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
  • Health Sciences › Medicine › Infectious Diseases › HIV/AIDS drug development and treatment
Keywords
HIV-1 capsid protein, capsid lattice, conformational heterogeneity, hydration shell, capsid stability, retroviral life cycle, hexagonal symmetry
MeSH terms
Amino Acid Sequence, Capsid, Molecular Sequence Data, HIV-1, Protein Structure, Secondary, Crystallography, X-Ray, gag Gene Products, Human Immunodeficiency Virus, Protein Multimerization

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