Efects of pontual deletions at linker regions of classical nuclear localisation sequences binding to Importina-±

• Grant number: 16/06694-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2016
• End date: December 31, 2016
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Principal Investigator: Ney Lemke
• Grantee: Thábatta Karollynne Estevam Nakamura
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

The spatial separation of the processes of transcription and translation present in eukaryotes provides efficient ways to control gene expression by requiring a selective transport between these two cellular compartments. A large number of protein is imported into the nucleus using the classical pathway nuclear import mediated by importin-±, solenoid protein which binds to the protein to be internalized by recognizing a signal sequence known as a nuclear localization sequence (NLS). In many cases, NLS is able to bind to the primary and secondary site of importin-± characterizing the bipartite NLS. The residues present between the primary and secondary sites represent the linker region of the NL. Previously, the data of the research group, which this project belongs, indicated the presence of stable contacts between the residues of the linker region of NLS nucleoplasmin bound to importin-±. The crystallography data importin-± complexes with NLS exhibit a linker with size of at least ten residues, so the current design aims to analyze the effect of deletions in the linker region on the stability of the connection between importin-± and NLS of nucleoplasmin. For this evaluation, we will use computer simulation technique known as Normal Mode Analysis, designed to measure collective movements and global conformational changes of protein systems. Thus, in the end it will be possible to analyze more effectively the fluctuations of the waste on the link between the proteins with deletion and importin-±, besides the evaluation of the types of interactions present in its interface. With the results of this project, we can assign more precisely the importance of this region in the route of classical nuclear import proteins.