|Entry||Database: PDB / ID: 6r4o|
|Title||Structure of a truncated adenylyl cyclase bound to MANT-GTP, forskolin and an activated stimulatory Galphas protein|
|Keywords||MEMBRANE PROTEIN / Adenylyl cyclase / G protein / MANT-GTP / forskolin|
|Function / homology|
Function and homology information
G alpha (z) signalling events / Glucagon signaling in metabolic regulation / PKA activation / PKA activation in glucagon signalling / Adenylate cyclase activating pathway / Adenylate cyclase inhibitory pathway / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (s) signalling events / Hedgehog 'off' state / corticotropin-releasing hormone receptor 1 binding ...G alpha (z) signalling events / Glucagon signaling in metabolic regulation / PKA activation / PKA activation in glucagon signalling / Adenylate cyclase activating pathway / Adenylate cyclase inhibitory pathway / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (s) signalling events / Hedgehog 'off' state / corticotropin-releasing hormone receptor 1 binding / cyclic nucleotide biosynthetic process / mu-type opioid receptor binding / adenylate cyclase-activating adrenergic receptor signaling pathway / adenylate cyclase activity / adenylate cyclase-activating dopamine receptor signaling pathway / positive regulation of cAMP-mediated signaling / D1 dopamine receptor binding / G-protein beta/gamma-subunit complex binding / beta-2 adrenergic receptor binding / heterotrimeric G-protein complex / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / adenylate cyclase activator activity / ionotropic glutamate receptor binding / G protein-coupled receptor binding / adenylate cyclase-activating G protein-coupled receptor signaling pathway / insulin-like growth factor receptor binding / positive regulation of GTPase activity / GTPase activity / GTP binding / nucleotide binding / integral component of plasma membrane / metal ion binding
G-protein alpha subunit, group S / G-protein alpha subunit / Adenylyl cyclase class-3/4/guanylyl cyclase / G protein alpha subunit, helical insertion / Adenylyl cyclase class-4/guanylyl cyclase, conserved site / P-loop containing nucleoside triphosphate hydrolase / Nucleotide cyclase / Adenylate and Guanylate cyclase catalytic domain / Guanylate cyclase signature. / Guanylate cyclase domain profile. ...G-protein alpha subunit, group S / G-protein alpha subunit / Adenylyl cyclase class-3/4/guanylyl cyclase / G protein alpha subunit, helical insertion / Adenylyl cyclase class-4/guanylyl cyclase, conserved site / P-loop containing nucleoside triphosphate hydrolase / Nucleotide cyclase / Adenylate and Guanylate cyclase catalytic domain / Guanylate cyclase signature. / Guanylate cyclase domain profile. / G-alpha domain profile. / Guanine nucleotide binding protein (G-protein), alpha subunit
Adenylyl CYclase family member (Acy-1)-like / Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
|Specimen source||Bos taurus (cattle)|
|Method||ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.2 Å|
|Authors||Qi, C. / Sorrentino, S. / Medalia, O. / Korkhov, V.M.|
|Funding support||Switzerland , 1件 |
Journal: Science / Year: 2019
Title: The structure of a membrane adenylyl cyclase bound to an activated stimulatory G protein.
Authors: Chao Qi / Simona Sorrentino / Ohad Medalia / Volodymyr M Korkhov /
Abstract: Membrane-integral adenylyl cyclases (ACs) are key enzymes in mammalian heterotrimeric GTP-binding protein (G protein)-dependent signal transduction, which is important in many cellular processes. ...Membrane-integral adenylyl cyclases (ACs) are key enzymes in mammalian heterotrimeric GTP-binding protein (G protein)-dependent signal transduction, which is important in many cellular processes. Signals received by the G protein-coupled receptors are conveyed to ACs through G proteins to modulate the levels of cellular cyclic adenosine monophosphate (cAMP). Here, we describe the cryo-electron microscopy structure of the bovine membrane AC9 bound to an activated G protein αs subunit at 3.4-angstrom resolution. The structure reveals the organization of the membrane domain and helical domain that spans between the membrane and catalytic domains of AC9. The carboxyl-terminal extension of the catalytic domain occludes both the catalytic and the allosteric sites of AC9, inducing a conformation distinct from the substrate- and activator-bound state, suggesting a regulatory role in cAMP production.
SummaryFull reportAbout validation report
|Date||Deposition: Mar 22, 2019 / Release: May 8, 2019Array|
|Structure viewer||Molecule: |
Downloads & links
A: Adenylate cyclase 9
B: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
-Protein/peptide , 2 types, 2 molecules A
|#1: Protein/peptide|| |
Mass: 170951.953 Da / Num. of mol.: 1
Details: Bovine AC9, residues 1-1250, tagged with 3C-YFP-twinStrep tag
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Bos taurus (cattle) / Gene: ADCY9, BOS_22626 / Cell line (production host): HEK293F / Production host: Homo sapiens (human) / References: UniProt: E1BM79
|#2: Protein/peptide|| |
Mass: 47003.801 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Bos taurus (cattle) / Gene: GNAS, GNAS1 / Cell line (production host): High Five / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: P04896
-Non-polymers , 5 types, 6 molecules
|#3: Chemical|| ChemComp-ONM / |
|#4: Chemical|| ChemComp-FOK / |
|#5: Chemical||#6: Chemical|| ChemComp-GSP / ||#7: Chemical|| ChemComp-MG / |
|Experiment||Method: ELECTRON MICROSCOPY|
|EM experiment||Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction|
Ncbi tax-ID: 9913 / Organism: Bos taurus (cattle)
|Buffer solution||pH: 8|
|Specimen||Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES|
|Vitrification||Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 278 K|
-Electron microscopy imaging
Model: Titan Krios / Image courtesy: FEI Company
|Microscopy||Model: FEI TITAN KRIOS|
|Electron gun||Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM|
|Electron lens||Mode: BRIGHT FIELDBright-field microscopy / Alignment procedure: COMA FREE|
|Specimen holder||Cryogen: NITROGEN / Model: FEI TITAN KRIOS AUTOGRID HOLDER|
|Image recording||Electron dose: 60 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 QUANTUM (4k x 4k) / Num. of grids imaged: 2 / Num. of real images: 10758 |
Details: Two datasets were merged using two different microscopes, using pixel size of 0.831 A/pix (4453 micrographs; 60 e-/A2) and 0.8544 A/pix (6305 micrographs; 45 e-/A2). Final dataset was scaled to 0.8544 A/pix.
|Software||Name: PHENIX / Version: 1.11.1_2575: / Classification: refinement|
|CTF correction||Type: NONE|
|Particle selection||Num. of particles selected: 1107881|
|Symmetry||Point symmetry: C1 (asymmetric)|
|3D reconstruction||Resolution: 4.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 142147 / Symmetry type: POINT|
|Atomic model building||B value: 110.92 / Protocol: AB INITIO MODEL / Space: REAL / Target criteria: Correlation coefficient|
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