title: Atomic Modeling of an Immature Retroviral Lattice Using Molecular Dynamics and Mutagenesis.
abstract: Defining the molecular interaction between Gag proteins in an assembled hexagonal lattice of immature retrovirus particles is crucial for elucidating the mechanisms of virus assembly and maturation. Recent advances in cryo-electron microscopy have yielded subnanometer structural information on the morphology of immature Gag lattices, making computational modeling and simulations feasible for investigating the Gag-Gag interactions at the atomic level. We have examined the structure of Rous sarcoma virus (RSV) using all-atom molecular dynamics simulations and in vitro assembly, to create the first all-atom model of an immature retroviral lattice. Microseconds-long replica exchange molecular dynamics simulation of the spacer peptide (SP)-nucleocapsid (NC) subdomains results in a six-helix bundle with amphipathic properties. The resulting model of the RSV Gag lattice shows features and dynamics of the capsid protein with implications for the maturation process, and confirms the stabilizing role of the upstream and downstream regions of Gag, namely p10 and SP-NC.
authors.affiliation: Department of Physics and Beckman Institute, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Boon Chong
authors.initials: BC
authors.lastname: Goh
authors.affiliation: Department of Physics and Beckman Institute, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Juan R
authors.initials: JR
authors.lastname: Perilla
authors.affiliation: Department of Microbiology and Immunology, Penn State University College of Medicine, Hershey, PA 17033, USA.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: England
authors.affiliation: Department of Microbiology and Immunology, Penn State University College of Medicine, Hershey, PA 17033, USA.
authors.forename: Katrina J
authors.initials: KJ
authors.lastname: Heyrana
authors.affiliation: Department of Microbiology and Immunology, Penn State University College of Medicine, Hershey, PA 17033, USA.
authors.forename: Rebecca C
authors.initials: RC
authors.lastname: Craven
authors.affiliation: Department of Physics and Beckman Institute, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA. Electronic address: kschulte@ks.uiuc.edu.
authors.forename: Klaus
authors.initials: K
authors.lastname: Schulten
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D003001:Cloning, Molecular; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D015683:Gene Products, gag / Q000737:chemistry* / Q000235:genetics; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D016296:Mutagenesis; D019251:Nucleocapsid / Q000737:chemistry* / Q000648:ultrastructure; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics; D052736:Rous sarcoma virus / Q000737:chemistry* / Q000648:ultrastructure; D019065:Virus Assembly / Q000235:genetics
chemical_list: D015683:Gene Products, gag; D011994:Recombinant Proteins