title: Dimerization of mammalian adenylate cyclases.
abstract: Mammalian adenylate cyclases are predicted to possess complex topologies, comprising two cassettes of six transmembrane-spanning motifs followed by a cytosolic, catalytic ATP-binding domain. Recent studies have begun to provide insights on the tertiary assembly of these proteins; crystallographic analysis has revealed that the two cytosolic domains dimerize to form a catalytic core, while more recent biochemical and cell biological analysis shows that the two transmembrane cassettes also associate to facilitate the functional assembly and trafficking of the enzyme. The older literature had suggested that adenylate cyclases might form higher order aggregates, although the methods used did not necessarily provide convincing evidence of biologically relevant events. In the present study, we have pursued this question by a variety of approaches, including rescue or suppression of function by variously modified molecules, coimmunoprecipitation and fluorescence resonance energy transfer (FRET) analysis between molecules in living cells. The results strongly suggest that adenylate cyclases dimerize (or oligomerize) via their hydrophobic domains. It is speculated that this divalent property may allow adenylate cyclases to participate in multimeric signaling assemblies.
authors.affiliation: Neuroscience Program University of Colorado Health Sciences Center, Denver, CO 80262, USA.
authors.forename: Chen
authors.initials: C
authors.lastname: Gu
authors.forename: James J
authors.initials: JJ
authors.lastname: Cali
authors.forename: Dermot M F
authors.initials: DM
authors.lastname: Cooper
mesh_terms: D000262:Adenylyl Cyclases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019281:Dimerization; D004735:Energy Transfer; D005453:Fluorescence; D049452:Green Fluorescent Proteins; D006367:HeLa Cells; D006801:Humans; D008164:Luminescent Proteins / Q000378:metabolism; D009154:Mutation; D011233:Precipitin Tests
chemical_list: D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins; D000262:Adenylyl Cyclases