3-DIMENSIONAL STRUCTURE OF THE HTLV-II MATRIX PROTEIN AND COMPARATIVE-ANALYSIS OF MATRIX PROTEINS FROM THE DIFFERENT CLASSES OF PATHOGENIC HUMAN RETROVIRUSES

The matrix protein performs similar roles in all retroviruses, initial ly directing membrane localization of the assembling viral particle an d subsequently forming a stable structural shell associated with the i nner surface of the mature viral membrane. Although conserved structur al elements are likely to perform these functions in all retroviral ma trix proteins, invariant motifs are not evident at the primary sequenc e level and three-dimensional structures have been available for only the primate lentiviral matrix proteins. We have therefore used NMR spe ctroscopy to determine the structure of the matrix protein from human T-cell leukemia virus type II (HTLV-II), a member of the human oncovir us subclass of retroviruses. A total of 577 distance restraints were u sed to build 20 refined models that superimpose with an rmsd of 0.71 A ngstrom for the backbone atoms of the structured regions. The globular HTLV-II matrix structure is composed of four alpha-helices and a 3(10 ) helix. Exposed basic residues near the C terminus of helix II form a putative membrane binding surface which could act in concert with the N-terminal myristoyl group to anchor the protein on the viral membran e surface. Clear structural similarities between the HTLV-II and HIV-1 matrix proteins suggest that the topology and exposed cationic membra ne binding surface are likely to be conserved features of retroviral m atrix proteins. (C) 1996 Academic Press Limited