CryoEM structure of MxB reveals a novel oligomerization interface critical for HIV restriction.
Sci Adv
; 3(9): e1701264, 2017 09.
Article
en En
| MEDLINE
| ID: mdl-28929138
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Fármacos Anti-VIH
/
Microscopía por Crioelectrón
/
Multimerización de Proteína
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Proteínas de Resistencia a Mixovirus
Límite:
Humans
Idioma:
En
Revista:
Sci Adv
Año:
2017
Tipo del documento:
Article
País de afiliación:
Estados Unidos