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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

The structure and properties of septin 3: a possible missing link in septin filament formation

Texto completo
Autor(es):
Macedo, Joci N. A. [1] ; Valadares, Napoleao F. [1] ; Marques, Ivo A. [1] ; Ferreira, Frederico M. [2] ; Damalio, Julio C. P. [1] ; Pereira, Humberto M. [1] ; Garratt, Richard C. [1] ; Araujo, Ana P. U. [1]
Número total de Autores: 8
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Ctr Biotecnol Mol Estrutural, Inst Fis Sao Carlos, Sao Carlos, SP - Brazil
[2] Univ Sao Paulo, Fac Med, Lab Imunol, Inst Coracao, Sao Paulo - Brazil
Número total de Afiliações: 2
Tipo de documento: Artigo Científico
Fonte: Biochemical Journal; v. 450, n. 1, p. 95-105, FEB 15 2013.
Citações Web of Science: 19
Resumo

The human genome codes for 13 members of a family of filament-forming GTP-binding proteins known as septins. These have been divided into four different subgroups on the basis of sequence similarity. The differences between the subgroups are believed to control their correct assembly into heterofilaments which have specific roles in membrane remodelling events. Many different combinations of the 13 proteins are theoretically possible and it is therefore important to understand the structural basis of specific filament assembly. However, three-dimensional structures are currently available for only three of the four subgroups. In the present study we describe the crystal structure of a construct of human SEPT3 which belongs to the outstanding subgroup. This construct (SEPT3-GC), which includes the GTP-binding and C-terminal domains, purifies as a nucleotide-free monomer, allowing for its characterization in terms of GTP-binding and hydrolysis. In the crystal structure, SEPT3-GC forms foreshortened filaments which employ the same NC and G interfaces observed in the heterotrimeric complex of human septins 2, 6 and 7, reinforcing the notion of `promiscuous' interactions described previously. In the present study we describe these two interfaces and relate the structure to its tendency to form monomers and its efficiency in the hydrolysis of GTP. The relevance of these results is emphasized by the fact that septins from the SEPT3 subgroup may be important determinants of polymerization by occupying the terminal position in octameric units which themselves form the building blocks of at least some heterofilaments. (AU)

Processo FAPESP: 06/57573-9 - Estudos bioquímicos e estruturais das septinas humanas SEPT3 e SEPT5 e identificação de parceiros protéicos
Beneficiário:Joci Neuby Alves Macedo
Linha de fomento: Bolsas no Brasil - Doutorado
Processo FAPESP: 08/58316-5 - Estudos cinéticos e funcionais das proteínas humanas da família septina
Beneficiário:Napoleão Fonseca Valadares
Linha de fomento: Bolsas no Brasil - Pós-Doutorado
Processo FAPESP: 98/14138-2 - Center for Structural Molecular Biotechnology
Beneficiário:Glaucius Oliva
Linha de fomento: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
Processo FAPESP: 08/57910-0 - Instituto Nacional de Biotecnologia Estrutural e Química Medicinal em Doenças Infecciosas - INBEQMeDI
Beneficiário:Richard Charles Garratt
Linha de fomento: Auxílio à Pesquisa - Temático