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

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

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

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 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.

Original languageEnglish
Pages (from-to)389-394
Number of pages6
JournalScience
Volume364
Issue number6438
DOIs
StatePublished - 1 Jan 2019

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