Subnanometer structures of HIV-1 envelope trimers on aldrithiol-2-inactivated virus particles.
2,2'-Dipyridyl
/ analogs & derivatives
Cell Line
Cryoelectron Microscopy
Disulfides
/ pharmacology
Electron Microscope Tomography
HIV Envelope Protein gp120
/ chemistry
HIV Envelope Protein gp41
/ chemistry
HIV Infections
/ virology
HIV-1
/ chemistry
Humans
Models, Molecular
Oxidants
/ pharmacology
Protein Conformation
/ drug effects
Protein Multimerization
/ drug effects
Solubility
Virion
/ chemistry
Journal
Nature structural & molecular biology
ISSN: 1545-9985
Titre abrégé: Nat Struct Mol Biol
Pays: United States
ID NLM: 101186374
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
received:
20
02
2020
accepted:
18
05
2020
pubmed:
1
7
2020
medline:
11
11
2020
entrez:
1
7
2020
Statut:
ppublish
Résumé
The HIV-1 envelope glycoprotein (Env) trimer, composed of gp120 and gp41 subunits, mediates viral entry into cells. Recombinant Env trimers have been studied structurally, but characterization of Env embedded in intact virus membranes has been limited to low resolution. Here, we deploy cryo-electron tomography and subtomogram averaging to determine the structures of Env trimers on aldrithiol-2 (AT-2)-inactivated virions in ligand-free, antibody-bound and CD4-bound forms at subnanometer resolution. Tomographic reconstructions document molecular features consistent with high-resolution structures of engineered soluble and detergent-solubilized Env trimers. One of three conformational states previously predicted by smFRET was not observed by cryo-ET, potentially owing to AT-2 inactivation. We did observe Env trimers to open in situ in response to CD4 binding, with an outward movement of gp120-variable loops and an extension of a critical gp41 helix. Overall features of Env trimer embedded in AT-2-treated virions appear well-represented by current engineered trimers.
Identifiants
pubmed: 32601441
doi: 10.1038/s41594-020-0452-2
pii: 10.1038/s41594-020-0452-2
pmc: PMC8138683
mid: NIHMS1698633
doi:
Substances chimiques
Disulfides
0
HIV Envelope Protein gp120
0
HIV Envelope Protein gp41
0
Oxidants
0
2,2'-dipyridyl disulfide
2127-03-9
2,2'-Dipyridyl
551W113ZEP
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
726-734Subventions
Organisme : NIAID NIH HHS
ID : R01 AI150560
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI150471
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM098859
Pays : United States
Organisme : NIH HHS
ID : S10 OD023603
Pays : United States
Organisme : CCR NIH HHS
ID : HHSN261200800001C
Pays : United States
Organisme : NCI NIH HHS
ID : HHSN261200800001E
Pays : United States
Organisme : NIAID NIH HHS
ID : R37 AI150560
Pays : United States
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