IMPLICATIONS FOR THE TRIMERIC STRUCTURE OF THE SIV MATRIX ANTIGEN. ^@Zihe Rao, ^@Elizabeth Fry, ^$Ian Jones, ^$Polly Roy and ^@David Stuart (^@The Laboratory of Molecular Biophysics, Rex Richards Building, South Parks Road, Oxford OX1 3QU, UK. ^$NERC Institute of Virology and Environmental Microbiology, Mansfield Road, Oxford OX1 3SR, UK.)

The crystal structure of the SIV matrix antigen (MA) has been determined at 100K (to dmin 2.1A) and 293K (to dmin 2.2A) by multiple isomorphous replacement and cross-averaging¹. The refined models (R-factors 18.0% and 16.4% for the 100K and 293K structures respectively) are highly similar (r.m.s deviation 0.18A between C_a atoms) but in some places the electron density is better defined for the 100K structure.

MA has roles delineated in targetting 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 corroborated 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 discussed

1)Z.Rao, A.Belyaev, E.Fry, P.Roy, I.Jones, D.Stuart. Nature 378, 743-747 (1995).

2)S.Blacklow, M.Lu, P.Kim. Biochemistry (in press).

3)C.Hill, D.Worthylake, D.Bancroft, A.Christensen, W.Sundquist. PNAS (in press).