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Cited by 372HIV Research and TreatmentEnzyme Structure and FunctionHIV/AIDS drug development and treatment

Atomic-level modelling of the HIV capsid

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Pornillos, Owen, Ganser-Pornillos, Barbie K., Yeager, Mark·2011·Nature
DOI 10.1038/nature09640PMC PMC3075868
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Abstract

The mature capsids of human immunodeficiency virus type 1 (HIV-1) and other retroviruses are fullerene shells, composed of the viral CA protein, that enclose the viral genome and facilitate its delivery into new host cells. Retroviral CA proteins contain independently folded amino (N)- and carboxy (C)-terminal domains (NTD and CTD) that are connected by a flexible linker. The NTD forms either hexameric or pentameric rings, whereas the CTD forms symmetric homodimers that connect the rings into a hexagonal lattice. We previously used a disulphide crosslinking strategy to enable isolation and crystallization of soluble HIV-1 CA hexamers. Here we use the same approach to solve the X-ray structure of the HIV-1 CA pentamer at 2.5 Å resolution. Two mutant CA proteins with engineered disulphides at different positions (P17C/T19C and N21C/A22C) converged onto the same quaternary structure, indicating that the disulphide-crosslinked proteins recapitulate the structure of the native pentamer. Assembly of the quasi-equivalent hexamers and pentamers requires remarkably subtle rearrangements in subunit interactions, and appears to be controlled by an electrostatic switch that favours hexamers over pentamers. This study completes the gallery of substructures describing the components of the HIV-1 capsid and enables atomic-level modelling of the complete capsid. Rigid-body rotations around two assembly interfaces appear sufficient to generate the full range of continuously varying lattice curvature in the fullerene cone.

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  • A crystal structure of a cross-linked pentameric assembly of HIV-1 CA confirmed that a pentamer could be obtained by removal of one copy of CA from a hexamer while keeping essentially the same protein-protein interactions.

    “A crystal structure of a cross-linked pentameric assembly of HIV-1 CA confirmed that a pentamer could be obtained by removal of one copy of CA from a hexamer while keeping essentially the same protein-protein interactions”

    From Retrovirus maturation-an extraordinary structural transformation (2016) · cites this paper as [57]

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Authors
Pornillos, O., Ganser-Pornillos, B. K., & Yeager, M.
Affiliations
Scripps Research Institute (US)
Corresponding author
Yeager, Mark
ORCID
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2011-01
Volume
469
Issue
7330
Pages
424-427
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
DOI
10.1038/nature09640
PMC
PMC3075868
OpenAlex
W1964022123
Cited by
372
References
5
Citations by year
2026: 6 · 2025: 18 · 2024: 13 · 2023: 15 · 2022: 20 · 2021: 34 · 2020: 25 · 2019: 30 · 2018: 22 · 2017: 18 · 2016: 35 · 2015: 34 · 2014: 25 · 2013: 33 · 2012: 32
FWCI
13.04
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
Funders
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-1 capsid, quaternary structure, electrostatic switch, capsid assembly, N-terminal domain, C-terminal domain
MeSH terms
Crystallization, Disulfides, Models, Molecular, Protein Binding, Rotation, HIV-1, Crystallography, X-Ray, Protein Structure, Quaternary, Capsid Proteins, Fullerenes, Protein Multimerization, Static Electricity

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