| Texto completo | |
| Autor(es): |
Silva do Vale Castro, Danielle Karoline
;
de Oliveira da Silva, Sabrina Matos
;
Pereira, Humberto D'Muniz
;
Alves Macedo, Joci Neuby
;
Leonardo, Diego Antonio
;
Valadares, Napoleao Fonseca
;
Kumagai, Patricia Suemy
;
Brandao-Neto, Jose
;
Ulian Araujo, Ana Paula
;
Garratt, Richard Charles
Número total de Autores: 10
|
| Tipo de documento: | Artigo Científico |
| Fonte: | IUCRJ; v. 7, p. 18-pg., 2020-05-01. |
| Resumo | |
Human septins 3, 9 and 12 are the only members of a specific subgroup of septins that display several unusual features, including the absence of a C-terminal coiled coil. This particular subgroup (the SEPT3 septins) are present in rod-like octameric protofilaments but are lacking in similar hexameric assemblies, which only contain representatives of the three remaining subgroups. Both hexamers and octamers can self-assemble into mixed filaments by end-to-end association, implying that the SEPT3 septins may facilitate polymerization but not necessarily function. These filaments frequently associate into higher order complexes which associate with biological membranes, triggering a wide range of cellular events. In the present work, a complete compendium of crystal structures for the GTP-binding domains of all of the SEPT3 subgroup members when bound to either GDP or to a GTP analogue is provided. The structures reveal a unique degree of plasticity at one of the filamentous interfaces (dubbed NC). Specifically, structures of the GDP and GTP gamma S complexes of SEPT9 reveal a squeezing mechanism at the NC interface which would expel a polybasic region from its binding site and render it free to interact with negatively charged membranes. On the other hand, a polyacidic region associated with helix alpha 5', the orientation of which is particular to this subgroup, provides a safe haven for the polybasic region when retracted within the interface. Together, these results suggest a mechanism which couples GTP binding and hydrolysis to membrane association and implies a unique role for the SEPT3 subgroup in this process. These observations can be accounted for by constellations of specific amino-acid residues that are found only in this subgroup and by the absence of the C-terminal coiled coil. Such conclusions can only be reached owing to the completeness of the structural studies presented here. (AU) | |
| Processo FAPESP: | 16/04658-9 - Determinantes estruturais para a especificidade de interação nas interfaces G e NC de septinas: validando as regras de substituição na montagem do filamento |
| Beneficiário: | Diego Antonio Leonardo Cabrejos |
| Modalidade de apoio: | Bolsas no Brasil - Doutorado |
| Processo FAPESP: | 16/19734-2 - Reconhecimento molecular em septinas: estudos da interface entre SEPT7 e SEPT12 |
| Beneficiário: | Danielle Karoline Silva Do Vale Castro |
| Modalidade de apoio: | Bolsas no Brasil - Mestrado |
| Processo FAPESP: | 08/58316-5 - Estudos cineticos e funcionais das proteinas humanas da familia septina |
| Beneficiário: | Napoleão Fonseca Valadares |
| Modalidade de apoio: | Bolsas no Brasil - 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 |
| Processo FAPESP: | 10/20290-5 - Estudos estruturais de complexos de septinas humanas |
| Beneficiário: | Joci Neuby Alves Macedo |
| Modalidade de apoio: | Bolsas no Brasil - Pós-Doutorado |
| Processo FAPESP: | 12/00268-0 - Estudos de Aspectos Estruturais Importantes na Montagem de Filamentos de Septinas Humanas |
| Beneficiário: | Sabrina Matos de Oliveira da Silva |
| Modalidade de apoio: | Bolsas no Brasil - Doutorado |