Skip to main content

Molecular Recognition of CXCR4 by a Dual Tropic HIV-1 gp120 V3 Loop

Author(s): Tamamis, Phanourios; Floudas, Christodoulos A

To refer to this page use:
Abstract: HIV-1 cell entry is initiated by the interaction of the viral envelope glycoprotein gp120 with CD4, and chemokine coreceptors CXCR4 and CCR5. The molecular recognition of CXCR4 or CCR5 by the HIV-1 gp120 is mediated through the V3 loop, a fragment of gp120. The binding of the V3 loop to CXCR4 or CCR5 determines the cell tropism of HIV-1 and constitutes a key step before HIV-1 cell entry. Thus, elucidating the molecular recognition of CXCR4 by the V3 loop is important for understanding HIV-1 viral infectivity and tropism, and for the design of HIV-1 inhibitors. We employed a comprehensive set of computational tools, predominantly based on free energy calculations and molecular-dynamics simulations, to investigate the molecular recognition of CXCR4 by a dual tropic V3 loop. We report what is, to our knowledge, the first HIV-1 gp120 V3 loop:CXCR4 complex structure. The computationally derived structure reveals an abundance of polar and nonpolar intermolecular interactions contributing to the HIV-1 gp120:CXCR4 binding. Our results are in remarkable agreement with previous experimental findings. Therefore, this work sheds light on the functional role of HIV-1 gp120 V3 loop and CXCR4 residues associated with HIV-1 coreceptor activity.
Publication Date: 17-Sep-2013
Citation: Tamamis, Phanourios, and Christodoulos A. Floudas. "Molecular Recognition of CXCR4 by a Dual Tropic HIV-1 gp120 V3 Loop." Biophysical Journal 105, no. 6 (2013): 1502-1514. doi: 10.1016/j.bpj.2013.07.049
DOI: doi:10.1016/j.bpj.2013.07.049
ISSN: 0006-3495
EISSN: 1542-0086
Pages: 1502 - 1514
Type of Material: Journal Article
Journal/Proceeding Title: Biophysical Journal
Version: Final published version. Article is made available in OAR by the publisher's permission or policy.

Items in OAR@Princeton are protected by copyright, with all rights reserved, unless otherwise indicated.