This research was supported by National Institutes of Health grants GM060170 and AI071798 to E.B.
Journal of Molecular Biology
Viral replication, Nuclear magnetic resonance, Human immunodeficiency virus type-1
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.
Alfadhli, Ayna (07/22/2011). "HIV-1 matrix protein binding to RNA". Journal of molecular biology (0022-2836), 410 (4), p. 653.