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Yorodumi- PDB-7pdh: structure of adenylyl cyclase 9 in complex with DARPin C4 and ATP-aS -
+Open data
-Basic information
Entry | Database: PDB / ID: 7pdh | |||||||||
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Title | structure of adenylyl cyclase 9 in complex with DARPin C4 and ATP-aS | |||||||||
Components |
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Keywords | SIGNALING PROTEIN / membrane protein / adenylyl cyclase / signalling transduction. | |||||||||
Function / homology | Function and homology information Adenylate cyclase activating pathway / Adenylate cyclase inhibitory pathway / PKA activation / adenylate cyclase / Hedgehog 'off' state / cAMP biosynthetic process / adenylate cyclase activity / G alpha (z) signalling events / adenylate cyclase-activating adrenergic receptor signaling pathway / adenylate cyclase-activating G protein-coupled receptor signaling pathway ...Adenylate cyclase activating pathway / Adenylate cyclase inhibitory pathway / PKA activation / adenylate cyclase / Hedgehog 'off' state / cAMP biosynthetic process / adenylate cyclase activity / G alpha (z) signalling events / adenylate cyclase-activating adrenergic receptor signaling pathway / adenylate cyclase-activating G protein-coupled receptor signaling pathway / in utero embryonic development / intracellular signal transduction / ATP binding / metal ion binding / plasma membrane / cytosol Similarity search - Function | |||||||||
Biological species | Bos taurus (cattle) synthetic construct (others) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4 Å | |||||||||
Authors | Qi, C. / Korkhov, V.M. | |||||||||
Funding support | 2items
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Citation | Journal: Nat Commun / Year: 2022 Title: Structural basis of adenylyl cyclase 9 activation. Authors: Chao Qi / Pia Lavriha / Ved Mehta / Basavraj Khanppnavar / Inayathulla Mohammed / Yong Li / Michalis Lazaratos / Jonas V Schaefer / Birgit Dreier / Andreas Plückthun / Ana-Nicoleta Bondar / ...Authors: 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 / 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 ...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. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7pdh.cif.gz | 131.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7pdh.ent.gz | 90.4 KB | Display | PDB format |
PDBx/mmJSON format | 7pdh.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7pdh_validation.pdf.gz | 703.6 KB | Display | wwPDB validaton report |
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Full document | 7pdh_full_validation.pdf.gz | 713.3 KB | Display | |
Data in XML | 7pdh_validation.xml.gz | 30.6 KB | Display | |
Data in CIF | 7pdh_validation.cif.gz | 44.3 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/pd/7pdh ftp://data.pdbj.org/pub/pdb/validation_reports/pd/7pdh | HTTPS FTP |
-Related structure data
Related structure data | 13338MC 7pd4C 7pd8C 7pddC 7pdeC 7pdfC 7pdgC C: citing same article (ref.) M: map data used to model this data |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 151142.875 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Bos taurus (cattle) / Production host: Homo sapiens (human) / References: UniProt: E1BM79 |
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#2: Protein | Mass: 16042.830 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) synthetic construct (others) / Production host: Escherichia coli (E. coli) |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
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Source (natural) |
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Source (recombinant) |
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Buffer solution | pH: 8 | ||||||||||||||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 48 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.19.2_4158: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: NONE | ||||||||||||||||||||||||
3D reconstruction | Resolution: 4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 170731 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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