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TitleThe structure of a membrane adenylyl cyclase bound to an activated stimulatory G protein.
Journal, issue, pagesScience, Vol. 364, Issue 6438, Page 389-394, Year 2019
Publish dateApr 26, 2019
AuthorsChao Qi / Simona Sorrentino / Ohad Medalia / Volodymyr M Korkhov /
PubMed AbstractMembrane-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.
External linksScience / PubMed:31023924
MethodsEM (single particle)
Resolution3.1 - 4.2 Å
Structure data

4719

6r3q

EMDB-4719, PDB-6r3q:
The structure of a membrane adenylyl cyclase bound to an activated stimulatory G protein
Method: EM (single particle) / Resolution: 3.4 Å

4721

6r4o

EMDB-4721, PDB-6r4o:
Structure of a truncated adenylyl cyclase bound to MANT-GTP, forskolin and an activated stimulatory Galphas protein
Method: EM (single particle) / Resolution: 4.2 Å

4722

6r4p

EMDB-4722, PDB-6r4p:
Structure of a soluble domain of adenylyl cyclase bound to an activated stimulatory G protein
Method: EM (single particle) / Resolution: 3.1 Å

EMDB-4723:
Soluble domain of membrane adenylyl cyclase bound to an activated stimulatory G protein, in the presence of MANT-GTP (SOL-M)
Method: EM (single particle) / Resolution: 4.2 Å

EMDB-4724:
Structure of a membrane adenylyl cyclase bound to an activated stimulatory G protein (SOL-C map)
Method: EM (single particle) / Resolution: 3.6 Å

EMDB-4725:
Structure of a membrane adenylyl cyclase bound to an activated stimulatory G protein (AC9-Gas-TM)
Method: EM (single particle) / Resolution: 3.6 Å

EMDB-4726:
The membrane portion of a membrane adenylyl cyclase bound to an activated stimulatory G protein (TM)
Method: EM (single particle) / Resolution: 3.6 Å

Chemicals

ChemComp-GSP:
5'-GUANOSINE-DIPHOSPHATE-MONOTHIOPHOSPHATE

ChemComp-MG:
Unknown entry

ChemComp-ONM:
3'-O-(N-METHYLANTHRANILOYL)-GUANOSINE-5'-TRIPHOSPHATE

ChemComp-FOK:
FORSKOLIN / Forskolin

ChemComp-MN:
Unknown entry

Source
  • bos taurus (cattle)
KeywordsMEMBRANE PROTEIN / adenylyl cyclase / G protein / occluded state / MANT-GTP / forskolin

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