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Nat Commun ; 11(1): 2663, 2020 05 29.
Artigo em Inglês | MEDLINE | ID: mdl-32471988

RESUMO

Endosomal sorting complexes for transport-III (ESCRT-III) assemble in vivo onto membranes with negative Gaussian curvature. How membrane shape influences ESCRT-III polymerization and how ESCRT-III shapes membranes is yet unclear. Human core ESCRT-III proteins, CHMP4B, CHMP2A, CHMP2B and CHMP3 are used to address this issue in vitro by combining membrane nanotube pulling experiments, cryo-electron tomography and AFM. We show that CHMP4B filaments preferentially bind to flat membranes or to tubes with positive mean curvature. Both CHMP2B and CHMP2A/CHMP3 assemble on positively curved membrane tubes. Combinations of CHMP4B/CHMP2B and CHMP4B/CHMP2A/CHMP3 are recruited to the neck of pulled membrane tubes and reshape vesicles into helical "corkscrew-like" membrane tubes. Sub-tomogram averaging reveals that the ESCRT-III filaments assemble parallel and locally perpendicular to the tube axis, highlighting the mechanical stresses imposed by ESCRT-III. Our results underline the versatile membrane remodeling activity of ESCRT-III that may be a general feature required for cellular membrane remodeling processes.


Assuntos
Complexos Endossomais de Distribuição Requeridos para Transporte/metabolismo , Membranas Artificiais , Estresse Mecânico , ATPases Associadas a Diversas Atividades Celulares/metabolismo , Fenômenos Bioquímicos , Microscopia Crioeletrônica , Humanos , Nanotubos , Polimerização , Ligação Proteica/fisiologia , Multimerização Proteica , ATPases Vacuolares Próton-Translocadoras/metabolismo
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