| Structural highlights
Function
[MX2_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 PubMed
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.
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.
References
- ↑ King MC, Raposo G, Lemmon MA. Inhibition of nuclear import and cell-cycle progression by mutated forms of the dynamin-like GTPase MxB. Proc Natl Acad Sci U S A. 2004 Jun 15;101(24):8957-62. Epub 2004 Jun 7. PMID:15184662 doi:http://dx.doi.org/10.1073/pnas.0403167101
- ↑ Goujon C, Moncorge O, Bauby H, Doyle T, Ward CC, Schaller T, Hue S, Barclay WS, Schulz R, Malim MH. Human MX2 is an interferon-induced post-entry inhibitor of HIV-1 infection. Nature. 2013 Oct 24;502(7472):559-62. doi: 10.1038/nature12542. Epub 2013 Sep 18. PMID:24048477 doi:http://dx.doi.org/10.1038/nature12542
- ↑ Liu Z, Pan Q, Ding S, Qian J, Xu F, Zhou J, Cen S, Guo F, Liang C. The interferon-inducible MxB protein inhibits HIV-1 infection. Cell Host Microbe. 2013 Oct 16;14(4):398-410. doi: 10.1016/j.chom.2013.08.015., Epub 2013 Sep 19. PMID:24055605 doi:http://dx.doi.org/10.1016/j.chom.2013.08.015
- ↑ Kane M, Yadav SS, Bitzegeio J, Kutluay SB, Zang T, Wilson SJ, Schoggins JW, Rice CM, Yamashita M, Hatziioannou T, Bieniasz PD. MX2 is an interferon-induced inhibitor of HIV-1 infection. Nature. 2013 Oct 24;502(7472):563-6. doi: 10.1038/nature12653. Epub 2013 Oct 13. PMID:24121441 doi:http://dx.doi.org/10.1038/nature12653
- ↑ Fribourgh JL, Nguyen HC, Matreyek KA, Alvarez FJ, Summers BJ, Dewdney TG, Aiken C, Zhang P, Engelman A, Xiong Y. Structural Insight into HIV-1 Restriction by MxB. Cell Host Microbe. 2014 Oct 8. pii: S1931-3128(14)00354-0. doi:, 10.1016/j.chom.2014.09.021. PMID:25312384 doi:http://dx.doi.org/10.1016/j.chom.2014.09.021
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