A point mutation uncouples transducin-alpha from the photoreceptor RGS and effector proteins.
A point mutation uncouples transducin-alpha from the photoreceptor RGS and effector proteins.
复制标题
点突变使转导蛋白-α 与光感受器 RGS 和效应蛋白解偶联。
DOI：
10.1046/j.1471-4159.2003.02103.x
复制
发表时间：
2003
影响因子：
4.7
通讯作者：
Artemyev,NikolaiO
中科院分区：
文献类型：
--
作者：
Natochin,Michael;Artemyev,NikolaiO
最近在优雅念珠菌Gq α蛋白EGL-30中发现了一种新的功能获得性突变R243 Q。EGL-30中对应于Arg 243的位置在异源三聚体G蛋白中是绝对保守的。该突变似乎是Gα亚基开关III区的第一个功能获得突变。为了研究R→Q突变的后果，我们将相应的R238 Q突变引入转导素样Gtα* 亚基。该突变体保留了与Gtβγ和视紫红质的完整相互作用，但鸟苷5 '-三磷酸（GTP）水解的kcat值降低了两倍。R238 Q的GT3活性没有被视觉GT3激活蛋白RGS 9 - 1的RGS结构域加速。此外，R238 Q在效应器功能中显示出显著的损害。我们的数据和transducin的晶体结构表明，R238 Q的内在GTP酶活性降低和RGS 9功能缺失的主要原因是Arg 238和Glu 39之间保守的离子接触的破坏，这显然稳定了GTP水解的过渡态。我们假设EGL-30中的R243 Q突变切断了Arg 243与Glu 43的离子相互作用，导致突变体被C. elegansRGS蛋白EAT-16.
A novel gain‐of‐function mutation, R243Q, has been recently identified in theCandida elegansGqα protein EGL‐30. The position corresponding to Arg243 in EGL‐30 is absolutely conserved among heterotrimeric G proteins. This mutation appears to be the first gain‐of‐function mutation in the switch III region of Gα subunits. To investigate consequences of the R→Q mutation we introduced the corresponding R238Q mutation into transducin‐like Gtα* subunit. The mutant retained intact interactions with Gtβγ and rhodopsin but exhibited a twofold reduction in the kcatvalue for guanosine 5'‐triphosphate (GTP) hydrolysis. The GTPase activity of R238Q was not accelerated by the RGS domain of the visual GTPase‐activating protein, RGS9‐1. In addition, R238Q displayed a significant impairment in the effector function. Our data and the crystal structures of transducin suggest that the major reason for the reduced intrinsic GTPase activity of R238Q and the lack of RGS9 function is the break of the conserved ionic contact between Arg238 and Glu39, which apparently stabilizes the transitional state for GTP hydrolysis. We hypothesize that the R243Q mutation in EGL‐30 severs the ionic interaction of Arg243 with Glu43, leading to a defective inactivation of the mutant by theC. elegansRGS protein EAT‐16.
登录
查看更多内容
细胞毒效应功能的编程与胸腺中 CD8(+) T 细胞分化期间的 CD4 消亡同时发生。
影响因子：
4.4
作者：
Bhandoola,A;Kithiganahalli,B;Granger,L;Singer,A
通讯作者：
Singer,A
人类 CD4 转基因拯救了 β2-微球蛋白缺陷小鼠的 CD4−CD8+ 细胞
DOI：
--
发表时间：
1994
期刊：
影响因子：
--
作者：
A. Baron;K. Hafen;H. von Boehmer
通讯作者：
H. von Boehmer
影响因子：
32.4
作者：
LINETTE, GP;GRUSBY, MJ;KORSMEYER, SJ
通讯作者：
KORSMEYER, SJ
影响因子：
4.4
作者：
T. Uchiyama;S. Broder;T. Waldmann
通讯作者：
T. Uchiyama;S. Broder;T. Waldmann
影响因子：
32.4
作者：
Sharp, LL;Schwarz, DA;Hedrick, SM
通讯作者：
Hedrick, SM