文章基本信息

标题：The helical domain of a G protein α subunit is a regulator of its effector
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作者：Wei Liu ; John K. Northup
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1998
卷号：95
期号：22
页码：12878-12883
DOI：10.1073/pnas.95.22.12878
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：The subunit (G) of heterotrimeric G proteins is a major determinant of signaling selectivity. The G structure essentially comprises a GTPase "Ras-like" domain (RasD) and a unique -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 G (Gt) and the closely related gustducin (Gg), but not Gi1, Gs, or Gq synergistically enhance guanosine 5'-{gamma}[-thio]triphosphate bound Gt (GtGTP{gamma}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. GtGDP 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 Gt with the PDE catalytic core may be caused by the HD moiety, and they indicate an independent site(s) for the HD moiety of Gt within the PDE catalytic core in addition to the sites for the inhibitory P{gamma} subunits. The HD moiety of GtGDP is an attenuator of the activated catalytic core, whereas in the presence of activated GtGTP{gamma}S the independently expressed HDt is a potent synergist. Rhodopsin catalysis of Gt activation enhances the PDE activation produced by subsaturating levels of Gt, suggesting a HD-moiety synergism from a transient conformation of Gt. 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.