title: Structural insight into the assembly of human anti-HIV dynamin-like protein MxB/Mx2.
abstract: Interferon (IFN) is a key component of the innate immune response to exogenous pathogens. Interferon increases the mRNA levels of interferon-stimulated genes (ISGs) in vivo, which is thought to account for its antiviral activity. Recent studies have indicated that human myxovirus resistance protein 2 (Mx2 or MxB), one of these ISGs, contributes to the inhibition of HIV-1 replication by interferon. MxB may bind to HIV-1 relatively late in the post-entry phase, and it leads to a reduced level of integrated viral DNA, thereby restricting HIV-1 infection. The N-terminal 91-aa domain of MxB and the assembly of MxB mediated by the Stalk domain have also been shown to be indispensible for MxB's anti-viral functions, but the mechanism involved has remained elusive. Here, we report the crystal structure (2.9Å) of the human MxB Stalk domain. MxB Stalk shows one dimer in the asymmetric unit. Each monomer contains a four-helix bundle. Interestingly, analyses of MxB dimer interfaces show that the majority of residues involved in the interface are not conserved between MxB and MxA, contributing to the building of a more stable MxB dimer. MxA and MxB Stalk domains share 46.7% sequence identity, and the structure of the MxA Stalk domain and the overall structure of MxB Stalk have a similar conformation. Our results indicate that although human Mx proteins share common structural characteristics, their dimerization strategies are unique, contributing to their unique contributions to viral restriction.
authors.affiliation: School of Life Sciences, Tianjin University, Tianjin 300072, China; Collaborative Innovation Center of Chemical Science and Engineering, Tianjin 300072, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Xu
authors.affiliation: School of Life Sciences, Tianjin University, Tianjin 300072, China; Collaborative Innovation Center of Chemical Science and Engineering, Tianjin 300072, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Kong
authors.affiliation: School of Life Sciences, Tianjin University, Tianjin 300072, China; Collaborative Innovation Center of Chemical Science and Engineering, Tianjin 300072, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Collaborative Innovation Center of Chemical Science and Engineering, Tianjin 300072, China; Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States; Institute of Virology and AIDS Research, First Hospital of Jilin University, 519 E Minzhu Ave, Changchun, Jilin Province 130061, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.affiliation: School of Life Sciences, Tianjin University, Tianjin 300072, China; Collaborative Innovation Center of Chemical Science and Engineering, Tianjin 300072, China. Electronic address: xiewei.xray@gmail.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Xie
authors.affiliation: School of Life Sciences, Tianjin University, Tianjin 300072, China; Collaborative Innovation Center of Chemical Science and Engineering, Tianjin 300072, China; Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States; Institute of Virology and AIDS Research, First Hospital of Jilin University, 519 E Minzhu Ave, Changchun, Jilin Province 130061, China. Electronic address: xfyu@tju.edu.cn.
authors.forename: Xiao-Fang
authors.initials: XF
authors.lastname: Yu
mesh_terms: D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray; D019281:Dimerization; D034281:Dynamins / Q000737:chemistry*; D015497:HIV-1 / Q000502:physiology; D006801:Humans; D007372:Interferons / Q000737:chemistry; D008969:Molecular Sequence Data; D064547:Myxovirus Resistance Proteins / Q000737:chemistry*; D017434:Protein Structure, Tertiary; D014779:Virus Replication
chemical_list: C579068:MX2 protein, human; D064547:Myxovirus Resistance Proteins; D007372:Interferons; D034281:Dynamins
keywords: Anti-HIV activity; Crystal structure; Dynamin-like protein; MxB; Stalk domain