Exploration of the intramolecular regulation of Tks4 scaffold protein
The gene of Tks4 scaffold protein (SH3PXD2B) was identified in 2005 by the research groups of professors Miklós Geiszt and András Lányi. The protein possesses 1 PX and 4 SH3 domains, and several proline-rich regions, and plays an important role in the integration of a number of signalling pathways. Homozygous loss-of-function mutations in SH3PXD2B gene lead to deletion or dysfunction of Tks4 protein, and lack of functional Tks4 causes a rare hereditary disease called Frank-ter Haar syndrome (FTHS). To develop an animal model for studying FTHS, László Buday’s group generated a Tks4 knockout mouse strain that recapitulates phenotypic features of FTHS. It is supposed that in quiescent cells Tks4 adopts a close protein conformation which may open up in response to different stimuli. Based on our previous results, it seems that domains localised on the N-terminal of the protein may form intramolecular interactions. The goal of our research project is to prove the existence of those intramolecular interactions by using different techniques, such as mutational analysis, NNR, SAXS, etc. Furthermore, it is very likely that protein kinases may phosphorylate specific residues in Tks4 leading to structural changes of the protein. Our research groups plan also to identify novel binding partners of the open-structured Tks4.
László Buday, Miklós Geiszt