Cryo-EM Structure of a Fully Glycosylated Soluble Cleaved HIV-1 Envelope Trimer

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 mi...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2013-12, Vol.342 (6165), p.1484-1490
Main Authors: Lyumkis, Dmitry, Julien, Jean-Philippe, de Val, Natalia, Cupo, Albert, Potter, Clinton S., Klasse, Per-Johan, Burton, Dennis R., Sanders, Rogier W., Moore, John P., Carragher, Bridget, Wilson, Ian A., Ward, Andrew B.
Format: Article
Language:English
Subjects:
AIDS Vaccines - chemistry
AIDS Vaccines - immunology
Antibodies
Antibodies, Neutralizing - chemistry
Antibodies, Viral - chemistry
Binding Sites
CD4 Antigens - chemistry
CD4 Antigens - immunology
Cryoelectron Microscopy
Crystal structure
env Gene Products, Human Immunodeficiency Virus - chemistry
env Gene Products, Human Immunodeficiency Virus - immunology
Epitopes
Glycoproteins
Glycosylation
HIV
HIV 1
Human immunodeficiency virus
Human immunodeficiency virus 1
Immunodominant Epitopes - chemistry
Immunodominant Epitopes - immunology
Medical research
Microscopy
Models, Molecular
mutation
Neutralizing antibodies
pathogenicity
Polysaccharides
Polysaccharides - chemistry
Protein Multimerization
Protein Structure, Quaternary
Protein Structure, Tertiary
Protein subunits
Trimers
Vaccination
vaccines
viruses
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Summary: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.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.1245627