title: Structure of a novel shoulder-to-shoulder p24 dimer in complex with the broad-spectrum antibody A10F9 and its implication in capsid assembly.
abstract: Mature HIV-1 viral particles assemble as a fullerene configuration comprising p24 capsid hexamers, pentamers and dimers. In this paper, we report the X-ray crystal structures of the p24 protein from natural HIV-1 strain (BMJ4) in complex with Fab A10F9, which recognizes a conserved epitope in the C-terminal domain of the BMJ4 p24 protein. Our structures reveal a novel shoulder-to-shoulder p24 dimerization mode that is mediated by an S-S bridge at C177. Consistent with these structures, the shoulder-to-shoulder dimer that was obtained from the BMJ4 strain was also observed in p24 proteins from other strains by the introduction of a cysteine residue at position 177. The potential biological significance was further validated by the introduction of a C177A mutation in the BMJ4 strain, which then displays a low infectivity. Our data suggest that this novel shoulder-to-shoulder dimer interface trapped by this unique S-S bridge could represent a physiologically relevant mode of HIV-1 capsid assembly during virus maturation, although Cys residue itself may not be critical for HIV-I replication.
authors.affiliation: National Institute of Diagnostics and Vaccine Development in Infectious Disease, School of Life Sciences, Xiamen University, Xiamen, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Gu
authors.forename: Fang
authors.initials: F
authors.lastname: Cao
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Wangheng
authors.initials: W
authors.lastname: Hou
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Choy-leong
authors.initials: CL
authors.lastname: Hew
authors.forename: Shaowei
authors.initials: S
authors.lastname: Li
authors.forename: Y Adam
authors.initials: YA
authors.lastname: Yuan
authors.forename: Ningshao
authors.initials: N
authors.lastname: Xia
mesh_terms: D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000378:metabolism*; D002213:Capsid / Q000378:metabolism*; D018360:Crystallography, X-Ray; D015483:HIV Antibodies / Q000378:metabolism*; D016655:HIV Core Protein p24 / Q000737:chemistry* / Q000378:metabolism; D015497:HIV-1 / Q000378:metabolism; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D012996:Solutions; D019065:Virus Assembly / Q000502:physiology*
chemical_list: D000911:Antibodies, Monoclonal; D015483:HIV Antibodies; D016655:HIV Core Protein p24; D007140:Immunoglobulin Fab Fragments; D012996:Solutions