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-Structure paper
タイトル | Structural basis of adenylyl cyclase 9 activation. |
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ジャーナル・号・ページ | Nat Commun, Vol. 13, Issue 1, Page 1045, Year 2022 |
掲載日 | 2022年2月24日 |
著者 | Chao Qi / Pia Lavriha / Ved Mehta / Basavraj Khanppnavar / Inayathulla Mohammed / Yong Li / Michalis Lazaratos / Jonas V Schaefer / Birgit Dreier / Andreas Plückthun / Ana-Nicoleta Bondar / Carmen W Dessauer / Volodymyr M Korkhov / |
PubMed 要旨 | 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 Gαs subunit and is autoinhibited by the ...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 Gαs subunit and is autoinhibited by the AC9 C-terminus. Although our recent structural studies of the AC9-Gαs 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 ATPαS, (iv) bound to Gαs and MANT-GTP. The artificial activator DARPin C4 partially activates AC9 by binding at a site that overlaps with the Gαs 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. |
リンク | Nat Commun / PubMed:35210418 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.8 - 4.9 Å |
構造データ | EMDB-13330, PDB-7pd4: EMDB-13331, PDB-7pd8: EMDB-13334, PDB-7pdd: EMDB-13335, PDB-7pde: EMDB-13336, PDB-7pdf: EMDB-13337, PDB-7pdg: EMDB-13338, PDB-7pdh: |
化合物 | ChemComp-GSP: ChemComp-MG: |
由来 |
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キーワード | SIGNALING PROTEIN / membrane protein / adenylyl cyclase / signalling transduction. |