Structural basis of transmembrane coupling of the HIV-1 envelope glycoprotein.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
08 05 2020
08 05 2020
Historique:
received:
26
11
2019
accepted:
16
04
2020
entrez:
10
5
2020
pubmed:
10
5
2020
medline:
18
8
2020
Statut:
epublish
Résumé
The prefusion conformation of HIV-1 envelope protein (Env) is recognized by most broadly neutralizing antibodies (bnAbs). Studies showed that alterations of its membrane-related components, including the transmembrane domain (TMD) and cytoplasmic tail (CT), can reshape the antigenic structure of the Env ectodomain. Using nuclear magnetic resonance (NMR) spectroscopy, we determine the structure of an Env segment encompassing the TMD and a large portion of the CT in bicelles. The structure reveals that the CT folds into amphipathic helices that wrap around the C-terminal end of the TMD, thereby forming a support baseplate for the rest of Env. NMR dynamics measurements provide evidences of dynamic coupling across the TMD between the ectodomain and CT. Pseudovirus-based neutralization assays suggest that CT-TMD interaction preferentially affects antigenic structure near the apex of the Env trimer. These results explain why the CT can modulate the Env antigenic properties and may facilitate HIV-1 Env-based vaccine design.
Identifiants
pubmed: 32385256
doi: 10.1038/s41467-020-16165-0
pii: 10.1038/s41467-020-16165-0
pmc: PMC7210310
doi:
Substances chimiques
Antibodies, Neutralizing
0
HIV Antibodies
0
env Gene Products, Human Immunodeficiency Virus
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2317Subventions
Organisme : NIGMS NIH HHS
ID : P41 GM132079
Pays : United States
Organisme : NIBIB NIH HHS
ID : P41 EB002026
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI127193
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI147884
Pays : United States
Organisme : NIH HHS
ID : S10 OD023513
Pays : United States
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