Publication Date:
2013-11-02
Description:
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 angstroms of a soluble, cleaved Env trimer that is stabilized and antigenically near-native (termed the BG505 SOSIP.664 gp140 trimer) in complex with a potent broadly neutralizing antibody, PGT122. The structure shows a prefusion 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 threefold 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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3886632/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3886632/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Julien, Jean-Philippe -- Cupo, Albert -- Sok, Devin -- Stanfield, Robyn L -- Lyumkis, Dmitry -- Deller, Marc C -- Klasse, Per-Johan -- Burton, Dennis R -- Sanders, Rogier W -- Moore, John P -- Ward, Andrew B -- Wilson, Ian A -- GM103310/GM/NIGMS NIH HHS/ -- P01 AI082362/AI/NIAID NIH HHS/ -- P01 AI82362/AI/NIAID NIH HHS/ -- P41 GM103310/GM/NIGMS NIH HHS/ -- P41RR001209/RR/NCRR NIH HHS/ -- R01 AI033292/AI/NIAID NIH HHS/ -- R01 AI084817/AI/NIAID NIH HHS/ -- R01 AI33292/AI/NIAID NIH HHS/ -- R37 AI036082/AI/NIAID NIH HHS/ -- R37 AI36082/AI/NIAID NIH HHS/ -- U54 GM094586/GM/NIGMS NIH HHS/ -- UM1 AI100663/AI/NIAID NIH HHS/ -- Y1-CO-1020/CO/NCI NIH HHS/ -- Y1-GM-1104/GM/NIGMS NIH HHS/ -- Canadian Institutes of Health Research/Canada -- New York, N.Y. -- Science. 2013 Dec 20;342(6165):1477-83. doi: 10.1126/science.1245625. Epub 2013 Oct 31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24179159" target="_blank"〉PubMed〈/a〉
Keywords:
Antibodies, Neutralizing/chemistry
;
Antibodies, Viral/chemistry
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Crystallography, X-Ray
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HIV Envelope Protein gp120/chemistry/immunology
;
HIV Envelope Protein gp41/chemistry/immunology
;
Humans
;
Protein Multimerization
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Protein Structure, Quaternary
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Recombinant Proteins/chemistry/immunology
;
Solubility
;
env Gene Products, Human Immunodeficiency Virus/*chemistry/immunology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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