Abstract

Small G-proteins are regarded as molecular switches that swing from an on state (GTP bound) to an off state (GDP bound). These switches are involved in regulating many cellular events as cell growth, proliferation, cytoskeletal remodeling, vesicle trafficking etc. In general, small G proteins are regulated by two classes of proteins. Proteins that accelerate the nucleotide exchange (GEFs) and hence shift the equilibrium to the on-state. Proteins that accelerate the hydrolysis of bound GTP (GAPs) and hence shift the equilibrium to the off-state. In my talk I will present two examples where the classical GEFs and GAPs regulation interplays with new signals and inputs. First I will talk about the crystal structure of Arf-ArfGAP complex in the transition state. This structure clarified a decade long debate of the catalytic mechanism. And lead us to discover a new calcium regulation mechanism that hints to a cross talk between the Arf and calcium signaling. Second I will present, using structural, biochemical and live cell imaging data how the Arl2/3•GTP can regulate the transport of farnesylated small G-proteins.