title: Structural Model of the Tubular Assembly of the Rous Sarcoma Virus Capsid Protein.
abstract: The orthoretroviral capsid protein (CA) assembles into polymorphic capsids, whose architecture, assembly, and stability are still being investigated. The N-terminal and C-terminal domains of CA (NTD and CTD, respectively) engage in both homotypic and heterotypic interactions to create the capsid. Hexameric turrets formed by the NTD decorate the majority of the capsid surface. We report nearly complete solid-state NMR (ssNMR) resonance assignments of Rous sarcoma virus (RSV) CA, assembled into hexamer tubes that mimic the authentic capsid. The ssNMR assignments show that, upon assembly, large conformational changes occur in loops connecting helices, as well as the short 310helix initiating the CTD. The interdomain linker becomes statically disordered. Combining constraints from ssNMR and cryo-electron microscopy (cryo-EM), we establish an atomic resolution model of the RSV CA tubular assembly using molecular dynamics flexible fitting (MDFF) simulations. On the basis of comparison of this MDFF model with an earlier-derived crystallographic model for the planar assembly, the induction of curvature into the RSV CA hexamer lattice arises predominantly from reconfiguration of the NTD-CTD and CTD trimer interfaces. The CTD dimer and CTD trimer interfaces are also intrinsically variable. Hence, deformation of the CA hexamer lattice results from the variable displacement of the CTDs that surround each hexameric turret. Pervasive H-bonding is found at all interdomain interfaces, which may contribute to their malleability. Finally, we find helices at the interfaces of HIV and RSV CA assemblies have very different contact angles, which may reflect differences in the capsid assembly pathway for these viruses.
authors.affiliation: Department of Physics, University of Central Florida , Orlando, Florida 32816, United States.
authors.forename: Jaekyun
authors.initials: J
authors.lastname: Jeon
authors.affiliation: Department of Physics, University of Central Florida , Orlando, Florida 32816, United States.
authors.forename: Xin
authors.initials: X
authors.lastname: Qiao
authors.affiliation: National High Magnetic Field Laboratory, Florida State University , Tallahassee, Florida 32310, United States.
authors.forename: Ivan
authors.initials: I
authors.lastname: Hung
authors.affiliation: School of Biological Sciences, University of Auckland , Private Bag 92019, Auckland 1142, New Zealand.
authors.forename: Alok K
authors.initials: AK
authors.lastname: Mitra
authors.affiliation: School of Biological Sciences, University of Auckland , Private Bag 92019, Auckland 1142, New Zealand.
authors.forename: Ambroise
authors.initials: A
authors.lastname: Desfosses
authors.affiliation: Department of Physics, University of Central Florida , Orlando, Florida 32816, United States.
authors.forename: Daniel
authors.initials: D
authors.lastname: Huang
authors.affiliation: National High Magnetic Field Laboratory, Florida State University , Tallahassee, Florida 32310, United States.
authors.forename: Peter L
authors.initials: PL
authors.lastname: Gor'kov
authors.affiliation: Department of Microbiology and Immunology, Penn State University College of Medicine , Hershey, Pennsylvania 17033, United States.
authors.forename: Rebecca C
authors.initials: RC
authors.lastname: Craven
authors.affiliation: School of Biological Sciences, University of Auckland , Private Bag 92019, Auckland 1142, New Zealand.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Kingston
authors.affiliation: National High Magnetic Field Laboratory, Florida State University , Tallahassee, Florida 32310, United States.
authors.forename: Zhehong
authors.initials: Z
authors.lastname: Gan
authors.affiliation: Department of Physics, Indiana University-Purdue University Indianapolis , Indianapolis, Indiana 46202, United States.
authors.forename: Fangqiang
authors.identifier: 0000-0001-6202-2262
authors.initials: F
authors.lastname: Zhu
authors.affiliation: Department of Physics, University of Central Florida , Orlando, Florida 32816, United States.
authors.forename: Bo
authors.identifier: 0000-0001-5589-2075
authors.initials: B
authors.lastname: Chen
mesh_terms: D036022:Capsid Proteins / Q000737:chemistry*; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D010316:Particle Size; D011487:Protein Conformation; D052736:Rous sarcoma virus / Q000737:chemistry*; D013499:Surface Properties
chemical_list: D036022:Capsid Proteins