3 years ago

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

Peijun Zhang, Frances J. D. Alvarez, Sjors H. W. Scheres, Shaoda He, Klaus Schulten, Juan R. Perilla, Alan N. Engelman, Sooin Jang

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.

Publisher URL: http://advances.sciencemag.org/cgi/content/short/3/9/e1701264

DOI: 10.1126/sciadv.1701264

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