title: Structural insight into HIV-1 restriction by MxB.
abstract: The myxovirus resistance (Mx) proteins are interferon-induced dynamin GTPases that can inhibit a variety of viruses. Recently, MxB, but not MxA, was shown to restrict HIV-1 by an unknown mechanism that likely occurs in close proximity to the host cell nucleus and involves the viral capsid. Here, we present the crystal structure of MxB and reveal determinants involved in HIV-1 restriction. MxB adopts an extended antiparallel dimer and dimerization, but not higher-ordered oligomerization, is critical for restriction. Although MxB is structurally similar to MxA, the orientation of individual domains differs between MxA and MxB, and their antiviral functions rely on separate determinants, indicating distinct mechanisms for virus inhibition. Additionally, MxB directly binds the HIV-1 capsid, and this interaction depends on dimerization and the N terminus of MxB as well as the assembled capsid lattice. These insights establish a framework for understanding the mechanism by which MxB restricts HIV-1.
authors.affiliation: Yale University, Molecular Biophysics and Biochemistry, New Haven, CT 06520, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Fribourgh
authors.affiliation: Yale University, Molecular Biophysics and Biochemistry, New Haven, CT 06520, USA.
authors.forename: Henry C
authors.initials: HC
authors.lastname: Nguyen
authors.affiliation: Dana-Farber Cancer Institute, Department of Cancer Immunology and AIDS, Boston, MA 02215, USA.
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Matreyek
authors.affiliation: University of Pittsburgh School of Medicine, Department of Structural Biology, Pittsburgh, PA 15260, USA.
authors.forename: Frances Joan D
authors.initials: FJD
authors.lastname: Alvarez
authors.affiliation: Yale University, Molecular Biophysics and Biochemistry, New Haven, CT 06520, USA.
authors.forename: Brady J
authors.initials: BJ
authors.lastname: Summers
authors.affiliation: Dana-Farber Cancer Institute, Department of Cancer Immunology and AIDS, Boston, MA 02215, USA.
authors.forename: Tamaria G
authors.initials: TG
authors.lastname: Dewdney
authors.affiliation: Vanderbilt University School of Medicine, Pathology, Microbiology and Immunology, Nashville, TN 37232-263, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Aiken
authors.affiliation: University of Pittsburgh School of Medicine, Department of Structural Biology, Pittsburgh, PA 15260, USA.
authors.forename: Peijun
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Dana-Farber Cancer Institute, Department of Cancer Immunology and AIDS, Boston, MA 02215, USA.
authors.forename: Alan
authors.initials: A
authors.lastname: Engelman
authors.affiliation: Yale University, Molecular Biophysics and Biochemistry, New Haven, CT 06520, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Xiong
mesh_terms: D002213:Capsid / Q000378:metabolism / Q000821:virology; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D005786:Gene Expression Regulation; D015497:HIV-1 / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D018613:Microscopy, Confocal; D064547:Myxovirus Resistance Proteins / Q000737:chemistry*; D011487:Protein Conformation; D055503:Protein Multimerization; D019065:Virus Assembly
chemical_list: C579068:MX2 protein, human; D064547:Myxovirus Resistance Proteins