6R4O

Structure of a truncated adenylyl cyclase bound to MANT-GTP, forskolin and an activated stimulatory Galphas protein

Summary for 6R4O

• Entry DOI: 10.2210/pdb6r4o/pdb
• EMDB information: 4721
• Descriptor: Adenylate cyclase 9, Guanine nucleotide-binding protein G(s) subunit alpha isoforms short, 3'-O-(N-METHYLANTHRANILOYL)-GUANOSINE-5'-TRIPHOSPHATE, ... (7 entities in total)
• Functional Keywords: adenylyl cyclase, g protein, mant-gtp, forskolin, membrane protein
• Biological source: Bos taurus (Bovine); More
• Total number of polymer chains: 2
• Total formula weight: 219696.01

Authors

Qi, C.,Sorrentino, S.,Medalia, O.,Korkhov, V.M. (deposition date: 2019-03-22, release date: 2019-05-08, Last modification date: 2024-05-15)

Primary citation

Qi, C.,Sorrentino, S.,Medalia, O.,Korkhov, V.M.
The structure of a membrane adenylyl cyclase bound to an activated stimulatory G protein.
Science, 364:389-394, 2019

PubMed 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. 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.

PubMed: 31023924
DOI: 10.1126/science.aav0778

Experimental method

ELECTRON MICROSCOPY (4.2 Å)