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

被引:45
作者
Alvarez, Frances J. D. [1 ,2 ]
He, Shaoda [3 ]
Perilla, Juan R. [4 ,5 ,10 ]
Jang, Sooin [2 ,6 ,7 ]
Schulten, Klaus [4 ,5 ]
Engelman, Alan N. [2 ,6 ,7 ]
Scheres, Sjors H. W. [3 ]
Zhang, Peijun [1 ,2 ,8 ,9 ]
机构
[1] Univ Pittsburgh, Sch Med, Dept Biol Struct, Pittsburgh, PA 15260 USA
[2] Univ Pittsburgh, Sch Med, Pittsburgh Ctr HIV Prot Interact, Pittsburgh, PA 15260 USA
[3] MRC Lab Mol Biol, Francis Crick Ave, Cambridge CB2 0QH, England
[4] Univ Illinois, Dept Phys, Urbana, IL 61801 USA
[5] Univ Illinois, Beckman Inst, Urbana, IL 61801 USA
[6] Dana Farber Canc Inst, Dept Canc Immunol & Virol, Boston, MA 02215 USA
[7] Harvard Med Sch, Dept Med, Boston, MA 02115 USA
[8] Univ Oxford, Div Struct Biol, Henry Wellcome Bldg Genom Med, Oxford OX3 7BN, England
[9] Electron Bioimaging Ctr, Diamond Light Source, Harwell Sci & Innovat Campus, Didcot OX11 0DE, Oxon, England
[10] Univ Delaware, Dept Chem & Biochem, Newark, DE 19716 USA
来源
SCIENCE ADVANCES | 2017年 / 3卷 / 09期
基金
英国医学研究理事会; 英国惠康基金;
关键词
MOLECULAR-DYNAMICS; HELICAL RECONSTRUCTION; VIRAL DETERMINANTS; PROTEIN; PREDICTION; GTPASE; MODEL; SPECIFICITY; RECOGNITION; HYDROLYSIS;
D O I
10.1126/sciadv.1701264
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 A 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.
引用
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页数:9
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