Specificity in the assembly of filaments Septins´s: the case of the Interface G between SEPT5 and SEPT8

• Grant number: 14/04233-2
• Support Opportunities: Scholarships in Brazil - Master
• Start date: May 01, 2014
• End date: April 30, 2016
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Principal Investigator: Richard Charles Garratt
• Grantee: Diego Antonio Leonardo Cabrejos
• Host Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil

Abstract

Septins are proteins that normally present GTPase activity, playing an important role in the maintenance of cell structure and serving as a scaffold for recruitment of other partner proteins. To perform their functions, septins form heterofilaments which are stabilized by interactions between the subunits through two types of interface, called G and NC. Their ectopic expression or inappropriate folding are associated with several diseases including Alzheimer's disease, Down's Syndrome, Parkinson's disease and a diversity of tumors. Understanding the exact molecular mechanisms that control the correct assembly of individual filaments and subsequently their packaging into higher order structures represents one of the greatest current challenges in the field of septin biochemistry. This process involves understanding the specific interfaces between septins along a filament (particularly given their tendency to interact in a promiscuous manner) as well as whether there is an intrinsic or extrinsic mechanism for assembly. For these studies, our group has been trying to crystallize physiologically relevant combinations of 3 or 4 septins. However, the production of such complexes with the expected stoichiometry, which are both pure and soluble is not a trivial task. This project proposes an alternative approach to simplify the challenge, which is to divide the problem such that each interface can be studied individually. Specifically, the focus of our study is the complex formed between septin Septin 5 and Septin 8 to better understand the interactions that stabilize the G interface formed between them. The knowledge gained from the development of this project and the expected results should contribute to understanding the structural basis for the correct assembly of a heterofilament.

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

CABREJOS, Diego Antonio Leonardo. Specificity in the assembly of Septins filaments: the case of the G interface between SEPT5 and SEPT8. 2016. Master's Dissertation - Universidade de São Paulo (USP). Instituto de Física de São Carlos (IFSC/BT) São Carlos.