An atomic model for the human septin hexamer by cryo-EM

Autor(es)

Mendonca, Deborah C. ^[1] ; Guimaraes, Samuel L. ^[1] ; Pereira, Humberto D'Muniz ^[1] ; Pinto, Andressa A. ^[1] ; de Farias, Marcelo A. ^[2] ; de Godoy, Andre S. ^[1] ; Araujo, Ana P. U. ^[1] ; van Heel, Marin ^[2] ; Portugal, V, Rodrigo ; Garratt, Richard C. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sao Carlos Inst Phys, Sao Carlos, SP - Brazil

^[2] V, CNPEM, Brazilian Nanotechnol Natl Lab, Campinas, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Journal of Molecular Biology; v. 433, n. 15 JUL 23 2021.
• Citações Web of Science: 0

Resumo

In order to form functional filaments, human septins must assemble into hetero-oligomeric rod-like particles which polymerize end-to-end. The rules governing the assembly of these particles and the subsequent filaments are incompletely understood. Although crystallographic approaches have been successful in studying the separate components of the system, there has been difficulty in obtaining high resolution structures of the full particle. Here we report a first cryo-EM structure for a hexameric rod composed of human septins 2, 6 and 7 with a global resolution of similar to 3.6 angstrom and a local resolution of between similar to 3.0 angstrom and similar to 5.0 angstrom. By fitting the previously determined high-resolution crystal structures of the component subunits into the cryo-EM map, we are able to provide an essentially complete model for the particle. This exposes SEPT2 NC-interfaces at the termini of the hexamer and leaves internal cavities between the SEPT6-SEPT7 pairs. The floor of the cavity is formed by the two alpha(0) helices including their polybasic regions. These are locked into place between the two subunits by interactions made with the alpha(5) and alpha(6) helices of the neighbouring monomer together with its polyacidic region. The cavity may serve to provide space allowing the subunits to move with respect to one another. The elongated particle shows a tendency to bend at its centre where two copies of SEPT7 form a homodimeric G-interface. Such bending is almost certainly related to the ability of septin filaments to recognize and even induce membrane curvature. (C) 2021 Elsevier Ltd. All rights reserved. (AU)

• Processo FAPESP: 17/15340-2 - EMU: aquisição de microscópio eletrônico de transmissão para criomicroscopia eletrônica de partículas isoladas - estabelecimento de uma instalação aberta de criomicroscopia eletrônica no CNPEM
• Beneficiário: Rodrigo Villares Portugal
• Modalidade de apoio: Auxílio à Pesquisa - Programa Equipamentos Multiusuários
• Processo FAPESP: 18/20209-5 - Estudos estruturais sobre a montagem de complexos de septinas por microscopia eletrônica de transmissão e análise de partículas isoladas
• Beneficiário: Deborah Cezar Mendonça
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 18/20816-9 - Análise de partícula única por crio-microscopia eletrônica de heterocomplexos de septinas
• Beneficiário: Samuel Leite Guimarães
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado
• Processo FAPESP: 14/15546-1 - Septinas: estudos comparativos visando correlacionar estrutura e função
• Beneficiário: Richard Charles Garratt
• Modalidade de apoio: Auxílio à Pesquisa - Temático