7PDH
structure of adenylyl cyclase 9 in complex with DARPin C4 and ATP-aS
Summary for 7PDH
| Entry DOI | 10.2210/pdb7pdh/pdb |
| EMDB information | 13337 13338 |
| Descriptor | Adenylate cyclase 9, DARPin C4 (2 entities in total) |
| Functional Keywords | membrane protein, adenylyl cyclase, signalling transduction., signaling protein |
| Biological source | Bos taurus (cattle) More |
| Total number of polymer chains | 2 |
| Total formula weight | 167185.70 |
| Authors | Qi, C.,Korkhov, V.M. (deposition date: 2021-08-05, release date: 2022-01-19, Last modification date: 2024-07-17) |
| Primary citation | Qi, C.,Lavriha, P.,Mehta, V.,Khanppnavar, B.,Mohammed, I.,Li, Y.,Lazaratos, M.,Schaefer, J.V.,Dreier, B.,Pluckthun, A.,Bondar, A.N.,Dessauer, C.W.,Korkhov, V.M. Structural basis of adenylyl cyclase 9 activation. Nat Commun, 13:1045-1045, 2022 Cited by PubMed Abstract: 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. PubMed: 35210418DOI: 10.1038/s41467-022-28685-y PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (4 Å) |
Structure validation
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