A short C-terminal peptide in Gγ regulates Gβγ signaling efficacy.
A short C-terminal peptide in Gγ regulates Gβγ signaling efficacy.
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DOI：
10.1091/mbc.e20-11-0750
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发表时间：
2021-08-01
影响因子：
3.3
通讯作者：
Karunarathne A
中科院分区：
文献类型：
--
作者：
Tennakoon M;Senarath K;Kankanamge D;Chadee DN;Karunarathne A
G蛋白β-γ（Gβγ）亚基通过Gγ中的羧基末端（CT）异戊二烯基锚定到质膜（PM）。这种相互作用对于PM定位和Gβγ的功能至关重要，允许GPCR-G蛋白信号传导进行。不同的Gγ家族有12个成员，我们最近发现，主要的Gβγ效应器的信号传导效力是Gγ型依赖性的。这种依赖性是由于Gγ的不同系列的膜相互作用能力。然而，允许Gβγ亚基表现出离散和不同范围的Gγ型依赖性膜亲和力的分子过程尚不清楚，并且不能仅用异戊二烯化的类型来解释。目前的工作探索了Gγ中膜相互作用CT残基的独特设计，作为这种Gγ型依赖性Gβγ信号传导的主要来源。尽管异戊烯化的类型不同，但结果显示PM处的信号传导功效，并且Gβγ的相关细胞行为由Gγ的5至6个残基的预异戊烯化区域中关键定位的特定氨基酸控制。所提供的Gγ-膜相互作用的分子图像可以解释细胞如何获得Gγ型依赖的G蛋白-GPCR信号以及Gβγ如何在不同的亚细胞区室中激发选择性信号。
G protein beta-gamma (Gβγ) subunits anchor to the plasma membrane (PM) through the carboxy-terminal (CT) prenyl group in Gγ. This interaction is crucial for the PM localization and functioning of Gβγ, allowing GPCR-G protein signaling to proceed. The diverse Gγ family has 12 members, and we have recently shown that the signaling efficacies of major Gβγ effectors are Gγ-type dependent. This dependency is due to the distinct series of membrane-interacting abilities of Gγ. However, the molecular process allowing for Gβγ subunits to exhibit a discrete and diverse range of Gγ-type–dependent membrane affinities is unclear and cannot be explained using only the type of prenylation. The present work explores the unique designs of membrane-interacting CT residues in Gγ as a major source for this Gγ-type–dependent Gβγ signaling. Despite the type of prenylation, the results show signaling efficacy at the PM, and associated cell behaviors of Gβγ are governed by crucially located specific amino acids in the five to six residue preprenylation region of Gγ. The provided molecular picture of Gγ–membrane interactions may explain how cells gain Gγ-type–dependent G protein-GPCR signaling as well as how Gβγ elicits selective signaling at various subcellular compartments.