Caracterização funcional e estrutural das septinas humanas 1, 6 e 8 / Functional and structural characterization of human septins 1, 6 and 8

AUTOR(ES)
DATA DE PUBLICAÇÃO

2010

RESUMO

Septins have a central domain which binds GTP (GTPase domain) and two other variable domains at their N- and C-termim Their principal characteristic is the ability to bind to other septins, thereby forming filaments. This is intimately related to their functions in cytokinesis, exocytosis, and apoptosis, among others. They are also directly or indirectly associated to pathological processes such as the Alzheimer disease and cancer. It has been suggested that one of its molecular functions may be to act as a "scaffold" protein to promote interactions among proteins. Thereby the functions of septins have turned out to be more diverse than initially predicted. Based on this our main objective here is lo identify the diversity of proteins thai interact with the human septins 6 and 8. We found that both interact with many other different septins, including almost all of them, except for septins of the same "group 6" (septins 6,8,10,11). The prey septins identified always contained the entire GTPase domain, indicating the importance of this domain for the observed interactions. Therefore, taking also into account data from the literature, we propose a model where the central unit of the trimeric septin is always occupied by septins of the group 6, specially septins 6 and 8. We also identified several other proteins to interact with septins 6 and 8, suggest involvement in processes such as cell division, metabolism, transcription, protein degradation, among others. The analysis of the expression of the septins 6,7,8 and 9 in mammalian cells suggests that they maybe localized to centrossomal structures, which are involved in cell division. Another study which involved full length as well as only the GTPase domain of Septin 1 showed that this septin is not found as a monomer but as a trimer/tetramer in solution. The GTPase domain as well as the presence of the bound nucleotide GTP, are fundamental for its multimerizalion and stability. In comparison to data from the literature, SEPT1 presents an elevated resistance to thermal denaturation. In summary, these and other data help us to understand the function of the septins and their relationship to cellular processes.

ASSUNTO(S)

gtp fosfoidrolases septinas yeast two-hybrid gtp phosphohydrolases septinas duplo-hibrido de levedura

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