7pd8

Structure of Adenylyl cyclase 9 in complex with DARPin C4 and MANT-GTP

spinqualitylabelsall models 7pd8, resolution 4.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7pd8 is a 2 chain structure with sequence from Bos taurus and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 4.2Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function E1BM79_BOVIN Publication Abstract from PubMed Adenylyl cyclase 9 (AC9) is a membrane-bound enzyme that converts ATP into cAMP. The enzyme is weakly activated by forskolin, fully activated by the G protein Galphas subunit and is autoinhibited by the AC9 C-terminus. Although our recent structural studies of the AC9-Galphas complex provided the framework for understanding AC9 autoinhibition, the conformational changes that AC9 undergoes in response to activator binding remains poorly understood. Here, we present the cryo-EM structures of AC9 in several distinct states: (i) AC9 bound to a nucleotide inhibitor MANT-GTP, (ii) bound to an artificial activator (DARPin C4) and MANT-GTP, (iii) bound to DARPin C4 and a nucleotide analogue ATPalphaS, (iv) bound to Galphas and MANT-GTP. The artificial activator DARPin C4 partially activates AC9 by binding at a site that overlaps with the Galphas binding site. Together with the previously observed occluded and forskolin-bound conformations, structural comparisons of AC9 in the four conformations described here show that secondary structure rearrangements in the region surrounding the forskolin binding site are essential for AC9 activation. Structural basis of adenylyl cyclase 9 activation.,Qi C, Lavriha P, Mehta V, Khanppnavar B, Mohammed I, Li Y, Lazaratos M, Schaefer JV, Dreier B, Pluckthun A, Bondar AN, Dessauer CW, Korkhov VM Nat Commun. 2022 Feb 24;13(1):1045. doi: 10.1038/s41467-022-28685-y. PMID:35210418 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also 3D Adenylyl cyclase 3D structures

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