On the roles of Mg in the activation of G proteins.
In this review, we highlight the evolution of our knowledge about the way Mg(2+) participates in the activation of heterotrimeric G proteins, beginning with its requirement in hormonal stimulation of fat cell adenylyl cyclase (1969) and ending with knowledge that incorporates information obtained from site directed mutagenesis and examination of the crystal structures of G proteins (2010). Our current view is that, as it seeks to fill its octahedral coordination shell, Mg acts as a keystone locking the G protein-α subunits into a conformation in which Gα dissociates from the Gβγ dimer, is competent in regulating effectors, and acquires GTPase activity. The latter is the result of moving the backbone carbonyl group of the Mg-coordinating threonine into a location in space that positions the hydrolytic water so as to facilitate the water's nucleophilic attack that leads to hydrolysis of the link between the β and γ phosphates of guanosine triphosphate (GTP). The role of the backbone carbonyl group of the Mg-coordinating threonine is equi-hierarchical with a similar and long-recognized role of the Switch II glutamine δ amide carbonyl group. Disruption of either leads to loss of GTPase activity.
Birnbaumer
Lutz
L
Laboratory of Neurobiology, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, NC27709, USA. birnbau1@niehs.nih.gov
Zurita
Adolfo R
AR
D000262:Adenylyl Cyclases / Q000378:metabolism; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000378:metabolism; D008274:Magnesium / Q000378:metabolism*; D015394:Molecular Structure; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015290:Second Messenger Systems
D021122:Protein Subunits; D006160:Guanosine Triphosphate; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D008274:Magnesium