title: A molecular determinant of human immunodeficiency virus particle assembly located in matrix antigen p17.
abstract: We report single-point mutations that are located in the matrix protein domain of the gag gene of human immunodeficiency virus type 1 and that prevent Gag particle formation. We show that mutations of p17 that abolish human immunodeficiency virus particle assembly also prevent the dimerization of p17 protein, as measured directly by a protein-protein binding assay. In the three-dimensional structure of p17, mutations that abolish dimerization are located in a single alpha helix that forms part of a fingerlike projection from one side of the molecule. Peptides derived from this region of p17 also reduce the level of p17 dimer when they are added to p17-expressing cells and compete for p17 self-association when present in protein-protein binding assays. We propose that the dimerization of the Gag precursor that occurs by the interdigitation of alpha helices on adjacent matrix molecules is a key stage in virion assembly and that the prevention of such an interaction is the molecular basis of particle misassembly.
authors.affiliation: Kitasato Institute, Kitasato University, Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Morikawa
authors.forename: T
authors.initials: T
authors.lastname: Kishi
authors.forename: W H
authors.initials: WH
authors.lastname: Zhang
authors.forename: M V
authors.initials: MV
authors.lastname: Nermut
authors.forename: D J
authors.initials: DJ
authors.lastname: Hockley
authors.forename: I M
authors.initials: IM
authors.lastname: Jones
mesh_terms: D001483:Base Sequence; D015683:Gene Products, gag / Q000737:chemistry*; D015497:HIV-1 / Q000737:chemistry*; D008969:Molecular Sequence Data; D017354:Point Mutation; D011498:Protein Precursors / Q000737:chemistry*; D017433:Protein Structure, Secondary; D013329:Structure-Activity Relationship; D014771:Virion / Q000737:chemistry*
chemical_list: D015683:Gene Products, gag; D011498:Protein Precursors; C059767:p55 gag precursor protein, Human immunodeficiency virus 1