Cryo-EM structure of a fully glycosylated soluble cleaved HIV-1 envelope trimer.

TitleCryo-EM structure of a fully glycosylated soluble cleaved HIV-1 envelope trimer.
Publication TypeJournal Article
Year of Publication2013
AuthorsLyumkis D, Julien J-P, de Val N, Cupo A, Potter CS, Klasse P-J, Burton DR, Sanders RW, Moore JP, Carragher B, Wilson IA, Ward AB
JournalScience
Volume342
Issue6165
Pagination1484-90
Date Published12/20/2013
ISSN1095-9203
KeywordsAIDS Vaccines, Antibodies, Neutralizing, Antibodies, Viral, Antigens, CD4, Binding Sites, Cryoelectron Microscopy, env Gene Products, Human Immunodeficiency Virus, Glycosylation, Immunodominant Epitopes, Models, Molecular, Polysaccharides, Protein Multimerization, Protein Structure, Quaternary, Protein Structure, Tertiary
Abstract

The HIV-1 envelope glycoprotein (Env) trimer contains the receptor binding sites and membrane fusion machinery that introduce the viral genome into the host cell. As the only target for broadly neutralizing antibodies (bnAbs), Env is a focus for rational vaccine design. We present a cryo-electron microscopy reconstruction and structural model of a cleaved, soluble Env trimer (termed BG505 SOSIP.664 gp140) in complex with a CD4 binding site (CD4bs) bnAb, PGV04, at 5.8 angstrom resolution. The structure reveals the spatial arrangement of Env components, including the V1/V2, V3, HR1, and HR2 domains, as well as shielding glycans. The structure also provides insights into trimer assembly, gp120-gp41 interactions, and the CD4bs epitope cluster for bnAbs, which covers a more extensive area and defines a more complex site of vulnerability than previously described.

DOI10.1126/science.1245627
Alternate JournalScience
PubMed ID24179160
Grant ListGM103310 / GM / NIGMS NIH HHS / United States
P01 AI082362 / AI / NIAID NIH HHS / United States
P01 AI82362 / AI / NIAID NIH HHS / United States
P41 GM103310 / GM / NIGMS NIH HHS / United States
R01 AI084817 / AI / NIAID NIH HHS / United States
R01 AI36082 / AI / NIAID NIH HHS / United States
UM1 AI100663 / AI / NIAID NIH HHS / United States
/ / Canadian Institutes of Health Research / Canada
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