Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody
Peter D. Kwong,Richard T. Wyatt,James E. Robinson,Raymond W. Sweet,Joseph Sodroski,Wayne A. Hendrickson,Wayne A. Hendrickson +6 more
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TLDR
The structure reveals a cavity-laden CD4–gp120 interface, a conserved binding site for the chemokine receptor, evidence for a conformational change upon CD4 binding, the nature of a CD4-induced antibody epitope, and specific mechanisms for immune evasion.Abstract:
The entry of human immunodeficiency virus (HIV) into cells requires the sequential interaction of the viral exterior envelope glycoprotein, gp120, with the CD4 glycoprotein and a chemokine receptor on the cell surface. These interactions initiate a fusion of the viral and cellular membranes. Although gp120 can elicit virus-neutralizing antibodies, HIV eludes the immune system. We have solved the X-ray crystal structure at 2.5 A resolution of an HIV-1 gp120 core complexed with a two-domain fragment of human CD4 and an antigen-binding fragment of a neutralizing antibody that blocks chemokine-receptor binding. The structure reveals a cavity-laden CD4-gp120 interface, a conserved binding site for the chemokine receptor, evidence for a conformational change upon CD4 binding, the nature of a CD4-induced antibody epitope, and specific mechanisms for immune evasion. Our results provide a framework for understanding the complex biology of HIV entry into cells and should guide efforts to intervene.read more
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Receptor Binding and Membrane Fusion in Virus Entry: The Influenza Hemagglutinin
John J. Skehel,Don C. Wiley +1 more
TL;DR: Comparisons to the soluble N-ethyl-maleimide-sensitive factor attachment protein receptor (SNARE) protein complex of vesicle fusion suggests that these molecules are all in the fusion-activated conformation and that the juxtaposition of the membrane anchor and fusion peptide, a recurring feature, is involved in the fused mechanism.
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HADDOCK: a protein-protein docking approach based on biochemical or biophysical information.
TL;DR: An approach called HADDOCK (High Ambiguity Driven protein-protein Docking) that makes use of biochemical and/or biophysical interaction data such as chemical shift perturbation data resulting from NMR titration experiments or mutagenesis data to drive the docking process.
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DC-SIGN, a dendritic cell-specific HIV-1-binding protein that enhances trans-infection of T cells
Teunis B.H. Geijtenbeek,Douglas S. Kwon,Ruurd Torensma,S.J. van Vliet,G.C.F. van Duijnhoven,J. Middel,I.L.M.H.A. Cornelissen,H.S.L.M. Nottet,Vineet N. KewalRamani,Dan R. Littman,Carl G. Figdor,Y. van Kooyk +11 more
TL;DR: It is proposed that DC-SIGN efficiently captures HIV-1 in the periphery and facilitates its transport to secondary lymphoid organs rich in T cells, to enhance infection in trans of these target cells.
Journal ArticleDOI
CHEMOKINE RECEPTORS AS HIV-1 CORECEPTORS: Roles in Viral Entry, Tropism, and Disease
TL;DR: In this paper, the chemokine receptors CXCR4 and CCR5, members of the G protein-coupled receptor superfamily, have been identified as the principal coreceptors for T cell line-tropic and macrophagetropic HIV-1 isolates, respectively.
Journal ArticleDOI
Rational Design of Envelope Identifies Broadly Neutralizing Human Monoclonal Antibodies to HIV-1
Xueling Wu,Zhi Yong Yang,Yuxing Li,Carl Magnus Hogerkorp,William R. Schief,Michael S. Seaman,Tongqing Zhou,Stephen D. Schmidt,Lan Wu,Ling Xu,Nancy S. Longo,Krisha McKee,Sijy O'Dell,Mark K. Louder,Diane Wycuff,Yu Feng,Martha Nason,Nicole A. Doria-Rose,Mark Connors,Peter D. Kwong,Mario Roederer,Richard T. Wyatt,Gary J. Nabel,John R. Mascola +23 more
TL;DR: Three broadly neutralizing antibodies are identified, isolated from an HIV-1–infected individual, that exhibited great breadth and potency of neutralization and were specific for the co-receptor CD4-binding site of the glycoprotein 120 (gp120), part of the viral Env spike.
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