|Support type:||Scholarships in Brazil - Doctorate|
|Effective date (Start):||July 01, 2012|
|Effective date (End):||August 31, 2015|
|Field of knowledge:||Biological Sciences - Biophysics - Molecular Biophysics|
|Principal Investigator:||Richard Charles Garratt|
|Grantee:||Sabrina Matos de Oliveira da Silva|
|Home Institution:||Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil|
Septins comprise a conserved family of filament forming guanine binding proteins. They have been associated with certain diseases in eukaryotes and are involved in a series of important cellular processes. These proteins are so named because of their role in septation during cell division in yeast, where a failure can lead to cell death or irregularities during the cell cycle. However, despite the importance of this class of proteins, little information in available concerning the details of their molecular functions. Particularly the role of GTP binding and hydrolysis as well as the mechanism of polymerization in the form of hetero-oligomers have yet to be completely established. The present proposal is centered on the structural analysis of novel septin complexes. The co-expression and crystallization of four complexes of septins will be attempted. The choice of combinations is based partly on the rules established by Kinoshita regarding the replacement of septins within a filament as well as the current literature and results of recent Y2H studies. The proposal is to perform the co-expression of complexes SEPT9-SEPT11-SEPT7-SEPT2, SEPT9-SEPT6-SEPT7; SEPT4-SEPT6-SEPT7 and SEPT4-SEPT8-SEPT7. It is anticipated that these combinations will allow us to investigate in detail the validity of Kinshita's rules. The determination of the crystal structures of these complexes will contribute significantly to our understanding of the structural details which control the formation of filaments by septins and how these proteins organize themselves into the correct structural arrangement, since so far only one structure of a heterocomplex at low resolution has been reported in the literature.