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The Helical Domain of a G Protein α Subunit is a Regulator of Its Effector
Wei Liu and John K. Northup
Proceedings of the National Academy of Sciences of the United States of America
Vol. 95, No. 22 (Oct. 27, 1998), pp. 12878-12883
Published by: National Academy of Sciences
Stable URL: http://www.jstor.org/stable/46162
Page Count: 6
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The α subunit (Gα ) of heterotrimeric G proteins is a major determinant of signaling selectivity. The Gα structure essentially comprises a GTPase ``Ras-like'' domain (RasD) and a unique α -helical domain (HD). We used the vertebrate phototransduction model to test for potential functions of HD and found that the HD of the retinal transducin Gα (Gα t) and the closely related gustducin (Gα g), but not Gα i1, Gα s, or Gα q synergistically enhance guanosine 5′-γ [-thio]triphosphate bound Gα t (Gα tGTPγ S) activation of bovine rod cGMP phosphodiesterase (PDE). In addition, both HDt and HDg, but not HDi1, HDs, or HDq attenuate the trypsin-activated PDE. Gα tGDP and HDt attenuation of trypsin-activated PDE saturate with similar affinities and to an identical 38% of initial activity. These data suggest that interaction of intact Gα t with the PDE catalytic core may be caused by the HD moiety, and they indicate an independent site(s) for the HD moiety of Gα t within the PDE catalytic core in addition to the sites for the inhibitory Pγ subunits. The HD moiety of Gα tGDP is an attenuator of the activated catalytic core, whereas in the presence of activated Gα tGTPγ S the independently expressed HDt is a potent synergist. Rhodopsin catalysis of Gα t activation enhances the PDE activation produced by subsaturating levels of Gα t, suggesting a HD-moiety synergism from a transient conformation of Gα t. These results establish HD-selective regulations of vertebrate retinal PDE, and they provide evidence demonstrating that the HD is a modulatory domain. We suggest that the HD works in concert with the RasD, enhancing the efficiency of G protein signaling.
Proceedings of the National Academy of Sciences of the United States of America © 1998 National Academy of Sciences