Journal
SCIENCE ADVANCES
Volume 3, Issue 9, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.1701264
Keywords
-
Categories
Funding
- NIH [GM082251, GM085043, GM104601, GM067887, OD019995, AI039394]
- Wellcome Trust Investigator Award [206422/Z/17/Z]
- UK Medical Research Council [MC UP A025 1013]
- NSF [OCI 07-25070, ACI-1238993]
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R37AI039394, R01AI039394] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [P41GM104601, P50GM082251, R01GM085043, R01GM067887] Funding Source: NIH RePORTER
- OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH [S10OD019995] Funding Source: NIH RePORTER
- Medical Research Council [MC_UP_A025_1013] Funding Source: researchfish
- MRC [MC_UP_A025_1013] Funding Source: UKRI
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available