title: Structural convergence between Cryo-EM and NMR reveals intersubunit interactions critical for HIV-1 capsid function.
abstract: Mature HIV-1 particles contain conical-shaped capsids that enclose the viral RNA genome and perform essential functions in the virus life cycle. Previous structural analysis of two- and three-dimensional arrays of the capsid protein (CA) hexamer revealed three interfaces. Here, we present a cryoEM study of a tubular assembly of CA and a high-resolution NMR structure of the CA C-terminal domain (CTD) dimer. In the solution dimer structure, the monomers exhibit different relative orientations compared to previous X-ray structures. The solution structure fits well into the EM density map, suggesting that the dimer interface is retained in the assembled CA. We also identified a CTD-CTD interface at the local three-fold axis in the cryoEM map and confirmed its functional importance by mutagenesis. In the tubular assembly, CA intermolecular interfaces vary slightly, accommodating the asymmetry present in tubes. This provides the necessary plasticity to allow for controlled virus capsid dis/assembly.
authors.affiliation: Department of Structural Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260, USA.
authors.forename: In-Ja L
authors.initials: IJ
authors.lastname: Byeon
authors.forename: Xin
authors.initials: X
authors.lastname: Meng
authors.forename: Jinwon
authors.initials: J
authors.lastname: Jung
authors.forename: Gongpu
authors.initials: G
authors.lastname: Zhao
authors.forename: Ruifeng
authors.initials: R
authors.lastname: Yang
authors.forename: Jinwoo
authors.initials: J
authors.lastname: Ahn
authors.forename: Jiong
authors.initials: J
authors.lastname: Shi
authors.forename: Jason
authors.initials: J
authors.lastname: Concel
authors.forename: Christopher
authors.initials: C
authors.lastname: Aiken
authors.forename: Peijun
authors.initials: P
authors.lastname: Zhang
authors.forename: Angela M
authors.initials: AM
authors.lastname: Gronenborn
mesh_terms: D036022:Capsid Proteins / Q000737:chemistry* / Q000378:metabolism; D020285:Cryoelectron Microscopy; D015497:HIV-1 / Q000737:chemistry* / Q000378:metabolism; D019906:Nuclear Magnetic Resonance, Biomolecular; D012367:RNA, Viral / Q000378:metabolism; D019065:Virus Assembly
chemical_list: D036022:Capsid Proteins; D012367:RNA, Viral