4h5j

Crystal Structure of the Guanine Nucleotide Exchange Factor Sec12 (P64 form)

spinqualitylabelsall models 4h5j, resolution 2.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4h5j is a 2 chain structure with sequence from Saccharomyces cerevisiae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.601Å Ligands: K, MSE Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed COPII-coated vesicles transport proteins and lipids from the endoplasmic reticulum to the Golgi. Crucial for the initiation of COPII coat assembly is Sec12, a guanine nucleotide exchange factor responsible for activating the small G protein Sar1. Once activated, Sar1/GTP binds to ER membranes and recruits COPII coat components (Sec23/24 and Sec13/31). Here, we report the 1.35 A resolution crystal structure of the catalytically active, 38-kDa cytoplasmic portion of Saccharomyces cerevisiae Sec12. Sec12 adopts a beta propeller fold. Conserved residues cluster around a loop we term the "K loop", which extends from the N-terminal propeller blade. Structure-guided site-directed mutagenesis, in conjunction with in vitro and in vivo functional studies, reveal that this region of Sec12 is catalytically essential, presumably because it makes direct contact with Sar1. Strikingly, the crystal structure also reveals that a single potassium ion stabilizes the K loop; bound potassium is, moreover, essential for optimum guanine nucleotide exchange activity in vitro. Thus, our results reveal a novel role for a potassium-stabilized loop in catalyzing guanine nucleotide exchange. The Structure of Sec12 Implicates Potassium Ion Coordination in Sar1 Activation.,McMahon C, Studer SM, Clendinen C, Dann GP, Jeffrey PD, Hughson FM J Biol Chem. 2012 Oct 29. PMID:23109340 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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