4li0 | pdb_00004li0
Crystal structure of GDP-bound Rab8:GRAB
Structural highlights
Function[RAB8A_HUMAN] May be involved in vesicular trafficking and neurotransmitter release. Together with RAB11A, RAB3IP, the exocyst complex, PARD3, PRKCI, ANXA2, CDC42 and DNMBP promotes transcytosis of PODXL to the apical membrane initiation sites (AMIS), apical surface formation and lumenogenesis. Together with MYO5B and RAB11A participates in epithelial cell polarization.[1] [2] [R3GEF_HUMAN] Guanine nucleotide exchange factor (GEF) which may activate RAB3A, a GTPase that regulates synaptic vesicle exocytosis. Promotes the exchange of GDP to GTP, converting inactive GDP-bound Rab proteins into their active GTP-bound form. May also activate RAB8A and RAB8B. Publication Abstract from PubMedSmall 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. References
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