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Interactions of HIV-1 proteins gp120 and Nef with cellular partners define a novel allosteric paradigm
Journal article   Peer reviewed

Interactions of HIV-1 proteins gp120 and Nef with cellular partners define a novel allosteric paradigm

Stephanie A Leavitt, Arne SchOn, Jeffrey C Klein, Uma Manjappara, Irwin M Chaiken and Ernesto Freire
Current protein & peptide science, v 5(1), pp 1-8
Feb 2004
DOI: https://doi.org/10.2174/1389203043486955
PMID: 14965316
Featured in Collection :   UN Sustainable Development Goals @ Drexel

Abstract

HIV-1 - metabolism Temperature HIV-1 - drug effects Allosteric Regulation Humans src Homology Domains - physiology HIV Envelope Protein gp120 - metabolism Thermodynamics Animals Gene Products, nef - chemistry Allosteric Site Drug Design Calorimetry, Differential Scanning HIV Infections - drug therapy Gene Products, nef - metabolism HIV Envelope Protein gp120 - chemistry nef Gene Products, Human Immunodeficiency Virus CD4 Antigens - metabolism
During the course of infection, a subset of HIV-1 proteins interacts with multiple cellular partners, sometimes in a hierarchical or sequential way. These proteins include those associated with the initial infection event, with the preparation of the cell for the replicative cycle of the virus and with the exit of new virions from the infected cell. It appears that the interactions of viral proteins with multiple cellular partners are mediated by the occurrence of ligand-induced conformational changes that direct the binding of these proteins to subsequent partners. Two of the most studied HIV-1 proteins that are known to interact with different cellular partners are gp120 and Nef. Here we discuss the interactions of these two proteins with their cellular partners and present new results indicating that the conformational changes undergone by these proteins define a novel allosteric paradigm. In the traditional view, conformational changes are thought to occur between well defined structural conformations of a protein. In gp120 and Nef, those changes involve conformations characterized by the presence of large regions devoid of stable secondary or tertiary structure. Those unstructured regions contain the binding determinants for subsequent partners and only become functionally competent by ligand-induced structuring or un-structuring of those regions. By switching binding epitopes between structured and unstructured conformations the binding affinity can be modulated by several orders of magnitude, thus effectively precluding binding against unwanted partners. A better understanding of these interactions would lead to improved strategies for inhibitor design against these viral targets.

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32 citations in Web of Science
30 citations in Scopus

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Collaboration types
Domestic collaboration
Web of Science research areas
Biochemistry & Molecular Biology
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