Journal article
Recognition of HIV-inactivating peptide triazoles by the recombinant soluble Env trimer, BG505 SOSIP.664
Proteins, structure, function, and bioinformatics, v 85(5), pp 843-851
May 2017
PMID: 28056499
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Peptide triazole (PT) antagonists interact with gp120 subunits of HIV-1 Env trimers to block host cell receptor interactions, trigger gp120 shedding, irreversibly inactivate virus and inhibit infection. Despite these enticing functions, understanding the structural mechanism of PT-Env trimer encounter has been limited. In this work, we combined competition interaction analysis and computational simulation to demonstrate PT binding to the recombinant soluble trimer, BG505 SOSIP.664, a stable variant that resembles native virus spikes in binding to CD4 receptor as well as known conformationally-dependent Env antibodies. Binding specificity and computational modeling fit with encounter through complementary PT pharmacophore Ile-triazolePro-Trp interaction with a 2-subsite cavity in the Env gp120 subunit of SOSIP trimer similar to that in monomeric gp120. These findings argue that PTs are able to recognize and bind a closed prefusion state of Env trimer upon HIV-1 encounter. The results provide a structural model of how PTs exert their function on virion trimeric spike protein and a platform to inform future antagonist design. Proteins 2017; 85:843-851. © 2016 Wiley Periodicals, Inc.
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Details
- Title
- Recognition of HIV-inactivating peptide triazoles by the recombinant soluble Env trimer, BG505 SOSIP.664
- Creators
- Kriti Acharya - Department of Biochemistry and Molecular Biology, Drexel University, Philadelphia, Pennsylvania, 19102Adel A Rashad - Department of Biochemistry and Molecular Biology, Drexel University, Philadelphia, Pennsylvania, 19102Francesca Moraca - Department of Chemical and Biological Engineering, Drexel University, Philadelphia, Pennsylvania, 19104Per Johan Klasse - Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, New York, 10065John P Moore - Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, New York, 10065Cameron Abrams - Department of Chemical and Biological Engineering, Drexel University, Philadelphia, Pennsylvania, 19104Irwin Chaiken - Department of Biochemistry and Molecular Biology, Drexel University, Philadelphia, Pennsylvania, 19102
- Publication Details
- Proteins, structure, function, and bioinformatics, v 85(5), pp 843-851
- Publisher
- Wiley; United States
- Grant note
- P01 GM056550 / NIGMS NIH HHS P01 AI110657 / NIAID NIH HHS R37 AI036082 / NIAID NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology; Chemical and Biological Engineering
- Web of Science ID
- WOS:000399380400004
- Scopus ID
- 2-s2.0-85015227505
- Other Identifier
- 991014877949104721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Biophysics