title: Crystal structure of an HIV assembly and maturation switch.
abstract: Virus assembly and maturation proceed through the programmed operation of molecular switches, which trigger both local and global structural rearrangements to produce infectious particles. HIV-1 contains an assembly and maturation switch that spans the C-terminal domain (CTD) of the capsid (CA) region and the first spacer peptide (SP1) of the precursor structural protein, Gag. The crystal structure of the CTD-SP1 Gag fragment is a goblet-shaped hexamer in which the cup comprises the CTD and an ensuing type II β-turn, and the stem comprises a 6-helix bundle. The β-turn is critical for immature virus assembly and the 6-helix bundle regulates proteolysis during maturation. This bipartite character explains why the SP1 spacer is a critical element of HIV-1 Gag but is not a universal property of retroviruses. Our results also indicate that HIV-1 maturation inhibitors suppress unfolding of the CA-SP1 junction and thereby delay access of the viral protease to its substrate.
authors.affiliation: Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, United States.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Wagner
authors.affiliation: Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, United States.
authors.forename: Kaneil K
authors.initials: KK
authors.lastname: Zadrozny
authors.affiliation: Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, United States.
authors.forename: Jakub
authors.initials: J
authors.lastname: Chrustowicz
authors.affiliation: Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, United States.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Purdy
authors.affiliation: Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, United States.|Department of Medicine, Division of Cardiovascular Medicine, University of Virginia Health System, Charlottesville, United States.
authors.forename: Mark
authors.initials: M
authors.lastname: Yeager
authors.affiliation: Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, United States.
authors.forename: Barbie K
authors.initials: BK
authors.lastname: Ganser-Pornillos
authors.affiliation: Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, United States.
authors.forename: Owen
authors.identifier: 0000-0001-9056-5002
authors.initials: O
authors.lastname: Pornillos
mesh_terms: D000595:Amino Acid Sequence; D002213:Capsid / Q000378:metabolism / Q000648:ultrastructure*; D036022:Capsid Proteins / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure*; D003001:Cloning, Molecular; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure*; D008958:Models, Molecular; D000072756:Protein Conformation, alpha-Helical; D000072757:Protein Conformation, beta-Strand; D000072417:Protein Domains; D055503:Protein Multimerization; D059748:Proteolysis; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D014771:Virion / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure*; D019065:Virus Assembly; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure*
chemical_list: D036022:Capsid Proteins; D011994:Recombinant Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus
keywords: HIV; assembly; biochemistry; biophysics; capsid; structural biology