%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% Joined ULB Machine Learning Group (MLG) and VIB/VUB Molecular Recognition unit (MoRe) S E M I N A R %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% Apologies for cross-postings. Please send it to interested colleagues and students. Thanks! Title: "Modular protein interaction domains - Evolution, Selectivity and Complexity" by: Dr. Piers D. Nash, The Ben May Department for Cancer Research The University of Chicago Chicago, IL, USA When: 14 February 2012 at 11:00 (until 12:30) Where: Building D Room D.005 (lower level) link to campus map: http://www.vub.ac.be/infoover/campussen/etterbeek.html Vrije Universiteit Brussel, Pleinlaan 2 1050 Bruxelles For those coming by car please email tlenaert_@_ulb.ac.be for a barcode to access the VUB campus. Abstract: Modular protein interaction domains (PIDs), such as the SH2 domain, are a common feature of many proteins, particularly those involved in cellular signal transduction. The SH2 domain recognizes phosphotyrosine modified peptide sequences, and in doing so couples tyrosine kinases to downstream signaling networks. We have examined the evolution of SH2 domains and find that they expand rapidly with the emergence of multicellularity and subsequent expansions concomitant with leaps in organismal complexity within the animal lineage. Increasing connectivity within and between SH2 proteins may underlie more highly interconnected and robust signal transduction networks. Yet the rapid evolutionary expansion of SH2 domains comes at some cost to selectivity so that the extant SH2 domains explore only a small region of the available peptide ligand sequence space. The ability of PIDs to nucleate highly selective interactions is essential for signal fidelity yet relies on limited peptid e sequence information. For instance, SH2 domains may appear to have simple binding motifs characterized by a few residues surrounding a phosphotyrosine (eg. pY-X-X-P/L). We have recently shown that by reading both permissive and non-permissive residues and longer regions of adjacent sequence, the SH2 domain is able to make use of a wider information channel to prescribe selective interactions. This results in a complex language for SH2 domain-peptide interactions in which the SH2 domain is readily able to distinguish physicochemically similar amino acids. Thus, despite evolutionary constraints, individual SH2 domains have distinct recognition profiles and exhibit a remarkable degree of selectivity. Speaker:Dr. Piers D. Nash is a world-renowned scientist who investigates protein-protein interactions involved in signal transduction, and the molecular mechanisms by which cells respond to external cues. After completing a postdoctoral position in the lab of Tony Pawson in Toronto, he became Assistant Professor in The Ben May Department for Cancer Research and a Scientist of the Comprehensive Cancer Center at The University of Chicago. His current work focuses on understanding the SH2 domain at a systems level and investigating the role of ubiquitination in controlling endocytosis and modulating signal transduction. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% MLG http://mlg.ulb.ac.be/ MORE http://more.vub.ac.be/ %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%