Small GTPase signaling hubs at the surface of cellular membranes in physiology and disease.

GEFs are generally multidomain proteins with conformational plasticity and often assemble in multisubunit complexes that interact with membranes to activate small GTPases attached to membranes. Insights regarding guanine nucleotide exchange from the structure of a DENN-domain protein complexed with its Rab GTPase substrate. GDP/GTP alternation is exquisitely regulated by two main classes of regulators: guanine nucleotide exchange factors or guanine nucleotide exchange factors (GEFs), which activate small GTPases by stimulating GDP/GTP exchange, and GTPase-activating proteins or GTPase-activating proteins (GAPs), which terminate their activity by stimulating the hydrolysis of GTP into GDP [[4]]. Most small GTPases carry post-translational modifications by lipids, whereby GDP/GTP alternation combines with cytosol/membrane alternation, itself regulated by guanine nucleotide dissociation inhibitors (GDIs) or functionally related proteins [[4]]. [Extracted from the article]