CryoET structures of immature HIV Gag reveal six-helix bundle.
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
16 04 2021
16 04 2021
Historique:
received:
06
11
2020
accepted:
18
03
2021
entrez:
17
4
2021
pubmed:
18
4
2021
medline:
6
8
2021
Statut:
epublish
Résumé
Gag is the HIV structural precursor protein which is cleaved by viral protease to produce mature infectious viruses. Gag is a polyprotein composed of MA (matrix), CA (capsid), SP1, NC (nucleocapsid), SP2 and p6 domains. SP1, together with the last eight residues of CA, have been hypothesized to form a six-helix bundle responsible for the higher-order multimerization of Gag necessary for HIV particle assembly. However, the structure of the complete six-helix bundle has been elusive. Here, we determined the structures of both Gag in vitro assemblies and Gag viral-like particles (VLPs) to 4.2 Å and 4.5 Å resolutions using cryo-electron tomography and subtomogram averaging by emClarity. A single amino acid mutation (T8I) in SP1 stabilizes the six-helix bundle, allowing to discern the entire CA-SP1 helix connecting to the NC domain. These structures provide a blueprint for future development of small molecule inhibitors that can lock SP1 in a stable helical conformation, interfere with virus maturation, and thus block HIV-1 infection.
Identifiants
pubmed: 33863979
doi: 10.1038/s42003-021-01999-1
pii: 10.1038/s42003-021-01999-1
pmc: PMC8052356
doi:
Substances chimiques
gag Gene Products, Human Immunodeficiency Virus
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
481Subventions
Organisme : NIGMS NIH HHS
ID : P50 GM082251
Pays : United States
Organisme : NIAID NIH HHS
ID : P50 AI150481
Pays : United States
Organisme : Wellcome Trust
ID : 203141/Z/16/Z
Pays : United Kingdom
Organisme : Medical Research Council
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/S003339/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 206422/Z/17/Z
Pays : United Kingdom
Organisme : Department of Health
Pays : United Kingdom
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