Journal Article

The structure of a membrane adenylyl cyclase bound to an activated stimulatory G protein

Sorrentino, Simona, Medalia, Ohad, Qi, Chao, Korkhov, Volodymyr M.

2019

Overview

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 as 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.

• Publisher: American Association for the Advancement of Science,The American Association for the Advancement of Science
• Subject: Adenosine / Adenosine monophosphate / Allosteric properties / Architecture / Catalysis / Cyclic AMP / Domains / Electron microscopy / Enzymatic activity / GTP-binding protein / Membranes / Microscopy / Proteins / Receptors / Signal processing / Signal transduction / Signaling / Substrates