Structure of the feline immunodeficiency virus matrix protein and the role of phosphatidylinositol-(4,5)-bisphosphate in membrane targeting.

摘要

The feline immunodeficiency virus (FIV) has become an interesting model for HIV-1 due to notable similarities in viral replication and pathogenesis. It has been established that the role of the FIV matrix protein is analogous to the role of the HIV-1 matrix protein. The matrix protein assists in viral penetration, transportation of the proviral integration complex across the nuclear envelope, and localization of the assembling virion to the cell membrane. Moreover, it has been reported that HIV-1 is targeted to the plasma membrane for viral assembly via an interaction between HIV-1 matrix and plasma membrane marker, phosphatidylinositol (4,5)-bisphosphate (PI(4,5)P2). However, the FIV assembly process remains unclear. To gain further insight into the function of the FIV matrix protein and the assembly process, we solved the three-dimensional structure of the FIV matrix protein, and explored the interaction between FIV matrix and PI(4,5)P2.;In this study we report the three-dimensional solution structure of the unmyristoylated FIV matrix protein using high resolution Nuclear Magnetic Resonance (NMR). The FIV matrix protein structure consists of five alpha-helices, and a long flexible basic loop that has been implicated in membrane binding. Our findings demonstrate that the three-dimensional structure of FIV matrix has a similar tertiary fold as primate lentiviruses, HIV-1, HIV-2 and SIV matrix.;To better understand the mechanism of viral assembly in FIV, we examined the role of PI(4,5)P2 in membrane targeting of FIV by studying the interaction between PI(4,5)P2 and the FIV matrix protein using NMR. Ours studies show that similar to HIV-1 MA, FIV MA binds to PI(4,5)P 2 facilitating membrane targeting.