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Sci Adv. 2017 Sep 15;3(9):e1701264. doi: 10.1126/sciadv.1701264. eCollection 2017 Sep.

CryoEM structure of MxB reveals a novel oligomerization interface critical for HIV restriction.

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Department of Structural Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260, USA.
Pittsburgh Center for HIV Protein Interactions, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260, USA.
MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
Department of Physics and Beckman Institute, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
Division of Structural Biology, Henry Wellcome Building for Genomic Medicine, University of Oxford, Headington, Oxford OX3 7BN, UK.
Electron Bio-Imaging Centre, Diamond Light Source, Harwell Science and Innovation Campus, Didcot OX11 0DE, UK.


Human dynamin-like, interferon-induced myxovirus resistance 2 (Mx2 or MxB) is a potent HIV-1 inhibitor. Antiviral activity requires both the amino-terminal region of MxB and protein oligomerization, each of which has eluded structural determination due to difficulties in protein preparation. We report that maltose binding protein-fused, full-length wild-type MxB purifies as oligomers and further self-assembles into helical arrays in physiological salt. Guanosine triphosphate (GTP), but not guanosine diphosphate, binding results in array disassembly, whereas subsequent GTP hydrolysis allows its reformation. Using cryo-electron microscopy (cryoEM), we determined the MxB assembly structure at 4.6 Å resolution, representing the first near-atomic resolution structure in the mammalian dynamin superfamily. The structure revealed previously described and novel MxB assembly interfaces. Mutational analyses demonstrated a critical role for one of the novel interfaces in HIV-1 restriction.

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