Signalling by small GTPases : from allosteric regulation to inhibition by small molecules
Ponente: Jacqueline Cherfils
CNRS and Ecole Normale Supérieure Paris-Saclay
Host: Xosé Bustelo
Salón de actos del Centro de Investigación del Cáncer
Lipidated small GTPases assemble protein complexes at the periphery of intracellular membranes to propagate signals and trigger actions, and their deregulation is associated with cancers and many other diseases. Guanine nucleotide exchange factors (GEFs), which activate small GTPase by stimulating GDP/GTP exchange, are key players in these processes. However, an integrated understanding of the contribution of the lipid bilayer to the efficiency and specificity of small GTPases machineries is still lacking. My lab addresses this question by combining structural biology, reconstitution of purified proteins in artificial membranes and interference by small molecules. I will present recent studies that illustrate the allosteric regulation of small GTPases and their GEFs by membranes and how this opens new routes for their inhibition by small molecules.