Signal Transduction in Protein Domains

Living cells feature complex protein networks involved in information signal transfer and processing events finely modulated by protein-protein interactions, often mediated by small modular domains such as the SH3 domains. The incidence of different SH3-binding motifs on the same target protein may be an intricate mechanism used by the cell to regulate SH3-mediated interactions. Often, modular interaction domains also occur in tandem on regulatory proteins. The CIN85/CMS family of adaptor proteins contains three highly similar N-terminal SH3 domains that are involved in a wide variety of intermolecular interactions with different targets. It has been hypothesized that such regulatory proteins can increase their affinity and specificity through co-operative binding involving multiple domains of the same or different kinds. The research focuses on the effect of the presence of a second or third domain on the affinity and specificity of the binding to the target. Moreover, recent research has shown that binding affinities change for both the SH2 and the SH3 domain of Fyn when either one of them is already linked to a peptide. Hence, in order to understand domain multiplicity one must also investigate the mechanics of intra- and inter-domain communication. This investigation is performed in collaboration with Tom Lenaerts, former member of the VIB Switch lab, and is a continuation of previous research activities in collaboration with members of the University of Granada.

Contact: prof. Nico van Nuland

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