Crystal Structure of a Soluble Cleaved HIV-1 Envelope Trimer.

TitleCrystal Structure of a Soluble Cleaved HIV-1 Envelope Trimer.
Publication TypeJournal Article
Year of Publication2013
AuthorsJulien J-P, Cupo A, Sok D, Stanfield RL, Lyumkis D, Deller MC, Klasse P-J, Burton DR, Sanders RW, Moore JP, Ward AB, Wilson IA
JournalScience
Date Published12/20/2013
ISSN1095-9203
Abstract

HIV-1 entry into CD4+ target cells is mediated by cleaved envelope glycoprotein (Env) trimers that have been challenging to characterize structurally. Here, we describe the crystal structure at 4.7 Å of an antigenically near-native, cleaved, stabilized, soluble Env trimer (termed BG505 SOSIP.664 gp140) in complex with a potent broadly neutralizing antibody, PGT122. The structure shows a pre-fusion state of gp41, the interaction between the component gp120 and gp41 subunits, and how a close association between the gp120 V1/V2/V3 loops stabilizes the trimer apex around the three-fold axis. The complete epitope of PGT122 on the trimer involves gp120 V1, V3 and several surrounding glycans. This trimer structure advances our understanding of how Env functions and is presented to the immune system, and provides a blueprint for structure-based vaccine design.

DOI10.1126/science.1245625
Alternate JournalScience
PubMed ID24179159
Grant ListP01 AI082362 / AI / NIAID NIH HHS / United States
R01 AI033292 / AI / NIAID NIH HHS / United States
R01 AI084817 / AI / NIAID NIH HHS / United States
R37 AI036082 / AI / NIAID NIH HHS / United States
UM1 AI100663 / AI / NIAID NIH HHS / United States
CHAVI-ID: 
1
Cover Picture: