Published In

Journal of Molecular Biology

Document Type

Article

Publication Date

7-22-2011

Subjects

Viral replication, Nuclear magnetic resonance, Human immunodeficiency virus type-1

Abstract

The matrix (MA) domain of the HIV-1 precursor Gag (PrGag) protein plays multiple roles in the viral replication cycle. One essential role is to target PrGag proteins to their lipid raft-associated phosphatidylinositol-(4,5)-bisphosphate (PI[4,5]P2) assembly sites at the plasma membranes (PMs) of infected cells. In addition to this role, several reports have implicated nucleic acid binding properties to retroviral MAs. Evidence indicates that RNA binding enhances the binding specificity of MA to PI(4,5)P2-containing membranes, and supports a hypothesis in which RNA binding to MA acts as a chaperone that protects MA from associating with inappropriate cellular membranes prior to PrGag delivery to PM assembly sites. To gain a better understanding of HIV-1 MA-RNA interactions, we have analyzed the interaction of HIV MA with RNA ligands that previously were selected for their high affinities to MA. Binding interactions were characterized via bead binding, fluorescence anisotropy, gel shift, and analytical ultracentrifugation methods. Moreover, MA residues that are involved in RNA binding were identified from NMR chemical shift data. Our results indicate that the MA RNA and PI(4,5)P2 binding sites overlap, and suggest models for Gag-membrane and Gag-RNA interactions, and for the HIV assembly pathway.

Description

This is the author’s version of a work that was accepted for publication in the Journal of Molecular Biology. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in J Mol Biol. 2011 July 22; 410(4): 653–666. doi:10.1016/j.jmb.2011.04.063.

http://www.sciencedirect.com/science/article/pii/S0022283611004967

DOI

10.1016/j.jmb.2011.04.063

Persistent Identifier

http://archives.pdx.edu/ds/psu/10047

Download

Share

COinS