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Cited by 523HIV Research and TreatmentEnzyme Structure and FunctionHIV/AIDS drug development and treatment

X-Ray Structures of the Hexameric Building Block of the HIV Capsid

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Pornillos, Owen, Ganser-Pornillos, Barbie K., Kelly, Brian N., Hua, Yuanzi, Whitby, Frank G., Stout, C. David, Sundquist, Wesley I., Hill, Christopher P. +1 more·2009·Cell
DOI 10.1016/j.cell.2009.04.063PMC PMC2840706
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Abstract

The mature capsids of HIV and other retroviruses organize and package the viral genome and its associated enzymes for delivery into host cells. The HIV capsid is a fullerene cone: a variably curved, closed shell composed of approximately 250 hexamers and exactly 12 pentamers of the viral CA protein. We devised methods for isolating soluble, assembly-competent CA hexamers and derived four crystallographically independent models that define the structure of this capsid assembly unit at atomic resolution. A ring of six CA N-terminal domains form an apparently rigid core, surrounded by an outer ring of C-terminal domains. Mobility of the outer ring appears to be an underlying mechanism for generating the variably curved lattice in authentic capsids. Hexamer-stabilizing interfaces are highly hydrated, and this property may be key to the formation of quasi-equivalent interactions within hexamers and pentamers. The structures also clarify the molecular basis for capsid assembly inhibition and should facilitate structure-based drug design strategies.

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  • 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 [44]

    The Introduction (page not provided) says CA proteins from different retroviruses share a common fold and that mature capsids are likely to have similar quaternary interactions. That supports a broadly conserved arrangement, but the paper presents conservation of capsid interactions as an inference, not an established finding. It also says high-resolution structures of full-length CA arrays were lacking, which is narrower than saying in-virus structures were lacking altogether. (LLM, conf=0.83)

    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 [44]

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  • 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 [44]

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Cites

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Cited by

Sorted by citations

Authors
Pornillos, O., Ganser-Pornillos, B. K., Kelly, B. N., Hua, Y., Whitby, F. G., Stout, C. D., Sundquist, W. I., Hill, C. P., & Yeager, M.
Affiliations
  • Scripps Research Institute (US)
  • University of Utah (US)
Corresponding author
Yeager, Mark
ORCID
Venue
Cell
Publisher
Elsevier BV
Published
2009-06
Volume
137
Issue
7
Pages
1282-1292
ISSN
0092-8674 (ISSN-L)
DOI
10.1016/j.cell.2009.04.063
PMC
PMC2840706
OpenAlex
W2117091532
Cited by
523
References
7
Citations by year
2026: 13 · 2025: 26 · 2024: 25 · 2023: 23 · 2022: 26 · 2021: 34 · 2020: 27 · 2019: 30 · 2018: 20 · 2017: 20 · 2016: 34 · 2015: 35 · 2014: 41 · 2013: 46 · 2012: 42
FWCI
14.58
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • University of Utah
  • National Institutes of Health
  • National Institute of General Medical Sciences (R01GM066087, P50GM082545)
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 capsid, capsid assembly, pentamer, structure-based drug design, viral genome packaging
MeSH terms
Models, Molecular, Polymers, HIV-1, Protein Structure, Tertiary, Crystallography, X-Ray, Capsid Proteins

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