Three-dimensional structure of the human immunodeficiency virus type 1 matrix protein.

摘要: The HIV-1 matrix protein forms an icosahedral shell associated with the inner membrane of mature virus. Genetic analyses have indicated that performs important functions throughout viral life-cycle, including anchoring transmembrane envelope on surface virus, assisting in penetration, transporting proviral integration complex across nuclear envelope, and localizing assembling virion to cell membrane. We now report three-dimensional structure recombinant protein, determined at high resolution by magnetic resonance (NMR) methods. is first retroviral be characterized structurally only fourth known structure. NMR signal assignments required recently developed triple-resonance (1H, 13C, 15N) methodologies because signals for 91% 132 assigned H alpha protons 74% 129 assignable backbone amide resonate within chemical shift ranges 0.8 p.p.m. 1 p.p.m., respectively. A total 636 Overhauser effect-derived distance restraints were employed geometry-based calculations, affording average 13.0 NMR-derived per residue experimentally constrained amino acids. An ensemble 25 refined geometry structures penalties (sum squares violations) 0.32 A2 or less individual violations under 0.06 was generated; best-fit superposition ordered heavy atoms relative mean atom positions afforded root-mean-square deviations 0.50 (+/- 0.08) A. folded composed five alpha-helices, a short 3(10) helical stretch, three-strand mixed beta-sheet. Helices I III helix pack about central (IV) form compact globular domain capped C-terminal (helix V) projects away from beta-sheet expose carboxyl-terminal residues essential early steps infectious cycle. Basic implicated binding localization cluster extruded cationic loop connects beta-strands 2. suggests both may mediated tertiary rather than simple linear determinants.