The HIV-1 Env gp120 Inner Domain Shapes the Phe43 Cavity and the CD4 Binding Site.
ADCC
CD4
CD4 binding site
CD4 mimetic
CD4mc
CRF01_AE
Env
HIV-1
Phe43 cavity
gp120
neutralization
Journal
mBio
ISSN: 2150-7511
Titre abrégé: mBio
Pays: United States
ID NLM: 101519231
Informations de publication
Date de publication:
26 05 2020
26 05 2020
Historique:
entrez:
28
5
2020
pubmed:
28
5
2020
medline:
10
4
2021
Statut:
epublish
Résumé
The HIV-1 envelope glycoproteins (Env) undergo conformational changes upon interaction of the gp120 exterior glycoprotein with the CD4 receptor. The gp120 inner domain topological layers facilitate the transition of Env to the CD4-bound conformation. CD4 engages gp120 by introducing its phenylalanine 43 (Phe43) in a cavity ("the Phe43 cavity") located at the interface between the inner and outer gp120 domains. Small CD4-mimetic compounds (CD4mc) can bind within the Phe43 cavity and trigger conformational changes similar to those induced by CD4. Crystal structures of CD4mc in complex with a modified CRF01_AE gp120 core revealed the importance of these gp120 inner domain layers in stabilizing the Phe43 cavity and shaping the CD4 binding site. Our studies reveal a complex interplay between the gp120 inner domain and the Phe43 cavity and generate useful information for the development of more-potent CD4mc.
Identifiants
pubmed: 32457241
pii: mBio.00280-20
doi: 10.1128/mBio.00280-20
pmc: PMC7251204
pii:
doi:
Substances chimiques
CD4 Antigens
0
HIV Envelope Protein gp120
0
Phenylalanine
47E5O17Y3R
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
Subventions
Organisme : NIAID NIH HHS
ID : P01 AI150471
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI129769
Pays : United States
Organisme : NIGMS NIH HHS
ID : P01 GM056550
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI131251
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI124982
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI145547
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI116274
Pays : United States
Organisme : NIAID NIH HHS
ID : R33 AI129017
Pays : United States
Organisme : NIAID NIH HHS
ID : R37 AI150590
Pays : United States
Organisme : CIHR
ID : 352417
Pays : Canada
Organisme : NIAID NIH HHS
ID : U01 AI150741
Pays : United States
Informations de copyright
Copyright © 2020 Prévost et al.
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