TCB Publications - Abstract

TCB Publications - Abstract

Frances J. D. Alvarez, Shaoda He, Juan R. Perilla, Sooin Jang, Klaus Schulten, Alan N. Engelman, Sjors H. W. Scheres, and Peijun Zhang. CryoEM structure of MxB reveals a novel oligomerization interface critical for HIV restriction. Science Advances, 3:e1701264, 2017. (PMC: PMC5600524)

ALVA2017 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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