4whj
From Proteopedia
Myxovirus Resistance Protein 2 (MxB)
Structural highlights
FunctionMX2_HUMAN Interferon-induced dynamin-like GTPase with potent antiviral activity against human immunodeficiency virus type 1 (HIV-1). Acts by targeting the viral capsid and affects the nuclear uptake and/or stability of the HIV-1 replication complex and the subsequent chromosomal integration of the proviral DNA. Exhibits antiviral activity also against simian immunodeficiency virus (SIV-mnd). May play a role in regulating nucleocytoplasmic transport and cell-cycle progression.[1] [2] [3] [4] Publication Abstract from PubMedThe 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. Structural Insight into HIV-1 Restriction by MxB.,Fribourgh JL, Nguyen HC, Matreyek KA, Alvarez FJ, Summers BJ, Dewdney TG, Aiken C, Zhang P, Engelman A, Xiong Y Cell Host Microbe. 2014 Oct 8. pii: S1931-3128(14)00354-0. doi:, 10.1016/j.chom.2014.09.021. PMID:25312384[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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