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Publication Abstract from PubMed

Small G-proteins (G) of the Ras-superfamily control the temporal and spatial coordination of intracellular signaling networks by acting as molecular on/off switches. Guanine nucleotide exchange factors (GEFs) regulate the activation of these G-proteins through catalytic replace-ment of guanosine diphosphate (GDP) by gua-nosine triphosphate (GTP). During nucleotide exchange, three distinct substrate-enzyme complexes occur: A ternary complex with GDP at the start of reaction (G:GDP:GEF), an intermediary nucleotide-free binary complex (G:GEF), and a ternary GTP-complex after productive G-protein activation (G:GTP:GEF). Here we show structural snapshots of the full nucleotide-exchange reaction sequence together with the G-protein substrates and products using Rabin8/GRAB (GEF) and Rab8 (G-protein) as a model system. Together with a thorough enzymatic characterization, our data provide a detailed view into the mechanism of Rabin8/GRAB mediated nucleotide exchange.

Intermediates in the Guanine Nucleotide Exchange Reaction of Rab8 Catalyzed by Rabin8/GRAB.,Guo Z, Hou X, Goody RS, Itzen A J Biol Chem. 2013 Sep 26. PMID:24072714^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.