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

DOI: 10.1126/sciadv.1701264 DOI Help

Authors: Frances J. D. Alvarez (University of Pittsburgh School of Medicine) , Shaoda He (MRC Laboratory of Molecular Biology) , Juan R. Perilla (University of Illinois at Urbana-Champaign) , Sooin Jang (University of Pittsburgh School of Medicine; Dana-Farber Cancer Institute; Harvard Medical School) , Klaus Schulten (University of Illinois at Urbana-Champaign) , Alan N. Engelman (University of Pittsburgh School of Medicine; Dana-Farber Cancer Institute; Harvard Medical School) , Sjors H. W. Scheres (MRC Laboratory of Molecular Biology) , Peijun Zhang (Diamond Light Source; University of Pittsburgh School of Medicine; University of Oxford)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Science Advances , VOL 3

State: Published (Approved)
Published: September 2017

Open Access Open Access

Abstract: 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.

Diamond Keywords: Viruses; Human Immunodeficiency Virus (HIV)

Subject Areas: Biology and Bio-materials

Technical Areas:

Added On: 26/09/2017 14:15


Discipline Tags:

Pathogens Infectious Diseases Health & Wellbeing Structural biology Life Sciences & Biotech

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