Implications for the trimeric structure of the SIV matrix antigen

Abstract

The crystal structure of the SIV matrix antigen (MA) has been determined at lOOK (to dmin 2.LK,.) and 293K (to dmin 2.2A) by multiple isomorphous replacement and cross-averaging l. The refined models (R-factors 18.0% and 16.4% for the lOOK and 293K structures respectively) m-e highly similar (r.m.s deviation 0.18A between Ca atoms) but in some places the electron density is better defined for the 1 OOK structure.MA has roles delineated in tm-getting Pr55 Gag to the plasma membrane, facilitating incorporation of the virus envelope glycoprotein (portions of which also form trimers2) and assembly of the Pr55 Gag shell. The structure revealed that when forced into a higher order assembly in the crystal, the MA subunits form a trimer. This oligomer may correspond to a basic building block in the Gag shell, explaining many of the biological properties of the protein . It has since been conoborated by a crystallographic analysis of its HIV homologue3 (50% sequence identity).The three-dimensional structure also suggests a model for retroviral Gag shell assembly. These implications and future possibilities for inhibitor design will be discussedWe will describe our progress towar-d a structure determination for cores of reovirus. Reovirus consists of a segmented ds RNA genome smTounded by two concentric protein shells. Wl1en the outer shell of reovirus is proteolytically removed, the viral core becomes active as a RNA processing machine.