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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >A regulator of G protein signaling interaction surface linked to effector specificity
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A regulator of G protein signaling interaction surface linked to effector specificity

机译：与效应子特异性相关的G蛋白信号传导相互作用表面的调节剂

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摘要

Proteins of the regulator of G protein signaling (RGS) family accelerate GTP hydrolysis by the o subunits (G.) of G proteins, leading to rapid recovery of signaling cascades. Many different RGS proteins can accelerate GTP hydrolysis by an individual G., and GTP hydrolysis rates of different G.s can be enhanced by the same R6S protein. Consequently, the mechanisms for specificity in RGS regulation and the residues involved remain unclear. Using the evolutionary trace (ET) method, we have identified a cluster of residues in the RGS domain that includes the RGS-G. binding interface and extends to include additional functionally important residues on the surface. One of these is within helix rr3, two are in as, and three are in the loop connecting αS and α6. A cluster of surface residues on G. previously identified by ET. and composed predominantly of residues from the switch lII region and helix α3, is spatially contiguous with the ET-identified residues in the RGS domain. This cluster includes residues proposed to interact with the y subunit of 6tαs effector, cGMP phosphodiesterase (PDEvi. The proximity of these clusters suggests that they form part of an interface between the effector and the RGS-G. complex. Sequence variations in these residues correlate with PDEγ effects on GTPase acceleration. Because ET identifies residues important for all mem- bers of a protein family, these residues likely form a general site for regulation of G protein-coupled signaling cascades, possibly by means of effector interactions.
机译：G蛋白信号转导（RGS）家族调节蛋白通过G蛋白的o亚基（G.）加速GTP水解，从而导致信号级联的快速恢复。许多不同的RGS蛋白可以通过单个G.加速GTP水解，而同一Gs6蛋白可以提高不同G.s的GTP水解速率。因此，RGS调控的特异性机制和涉及的残基仍不清楚。使用进化跟踪（ET）方法，我们已经在RGS域中鉴定了一个包括RGS-G的残基簇。结合界面并延伸到表面上包括其他功能上重要的残基。其中之一在螺旋rr3内，两个在as内，三个在连接αS和α6的回路中。先前由ET鉴定的G.上的表面残留物簇。且主要由开关II区和螺旋α3的残基组成，在空间上与RGS结构域中的经ET鉴定的残基相邻。该簇包含拟与6tαs效应子cGMP磷酸二酯酶（PDEvi）的y亚基相互作用的残基。这些簇的邻近性表明它们形成了效应子与RGS-G。复合体之间的界面的一部分。这些残基中的序列变异相互关联由于ET识别出对蛋白质家族的所有成员都重要的残基，因此这些残基很可能形成了调控G蛋白偶联信号级联的一般位点，可能是通过效应子相互作用。

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