RhoGDIα Acetylation at K127 and K141 Affects Binding toward Nonprenylated RhoA.
RhoGDIα Acetylation at K127 and K141 Affects Binding toward Nonprenylated RhoA.
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K127 和 K141 处的 RhoGDIα 乙酰化影响与非异戊二烯化 RhoA 的结合
DOI：
10.1021/acs.biochem.5b01242
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发表时间：
2016
期刊：
影响因子：
2.9
通讯作者：
Lammers
中科院分区：
文献类型：
--
作者：
Kuhlmann;Wroblowski;Scislowski;Lammers
Rho蛋白是细胞骨架的主要调节者。与大多数RAS相关蛋白一样，它们在GTP结合的活性构象和GDP结合的非活性构象之间切换。Rho蛋白通过C-末端半胱氨酸残基上的多碱区和戊烯基团靶向质膜。为了将Rho蛋白分布在细胞内，分子伴侣RhoGDIα与预酯化的Rho蛋白结合，形成一个主要装载GDP的Rho胞浆池。大多数研究都描述了Prenylated Rho蛋白与RhoGDIα的相互作用。然而，RhoGDIα也被证明与具有生理上相关的微摩尔亲和力的非戊烯基化的Rho蛋白结合。最近，人们发现RhoGDIα是翻译后赖氨酸乙酰化的靶点。对于K141位点，假设乙酰化可能导致哺乳动物细胞中丝状肌动蛋白和丝状足的形成水平增加。赖氨酸乙酰化与非戊烯基化的RhoA相互作用的功能后果还没有被研究。在这里，我们用生化和生物物理相结合的方法报道了RhoGDIα免疫球蛋白结构域中赖氨酸K127和K141上的赖氨酸乙酰化干扰了非戊烯基化的RhoA的相互作用。我们测定了双乙酰化蛋白质RhoGDIα与RhoA·Gdp的第一个晶体结构。我们发现，RhoA的C末端采用不同的构象，与RhoGDIβ免疫球蛋白结构域形成分子间α-Sheet。
Rho proteins are major regulators of the cytoskeleton. As most Ras-related proteins, they switch between an active, GTP-bound and an inactive, GDP-bound conformation. Rho proteins are targeted to the plasma membrane via a polybasic region and a prenyl group attached to a C-terminal cysteine residue. To distribute Rho proteins in the cell, the molecular chaperone RhoGDIα binds to the prenylated Rho proteins forming a cytosolic pool of mainly GDP-loaded Rho. Most studies characterized the interaction of prenylated Rho proteins and RhoGDIα. However, RhoGDIα was also shown to bind to nonprenylated Rho proteins with physiologically relevant micomolar affinities. Recently, it was discovered that RhoGDIα is targeted by post-translational lysine acetylation. For one site, K141, it was hypothesized that acetylation might lead to increased levels of formation of filamentous actin and filopodia in mammalian cells. The functional consequences of lysine acetylation for the interplay with nonprenylated RhoA have not been investigated. Here, we report that lysine acetylation at lysines K127 and K141 in the RhoGDIα immunoglobulin domain interferes with the interaction toward nonprenylated RhoA using a combined biochemical and biophysical approach. We determined the first crystal structure of a doubly acetylated protein, RhoGDIα, in complex with RhoA·GDP. We discover that the C-terminus of RhoA adopts a different conformation forming an intermolecular β-sheet with the RhoGDIα immunoglobulin domain.
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RhoGDI 促进香叶基香叶基转移酶-I 介导的 RhoA 异戊二烯化。
影响因子：
3.1
作者：
Z. Tnimov;D. Abankwa;K. Alexandrov
通讯作者：
K. Alexandrov
影响因子：
14.8
作者：
Ismail, Shehab A.;Chen, Yong-Xiang;Wittinghofer, Alfred
通讯作者：
Wittinghofer, Alfred
一致。
DOI：
10.1097/iae.0000000000001602
发表时间：
2017
期刊：
Retina (Philadelphia, Pa.)
影响因子：
--
作者：
Todorich,Bozho;Thanos,Aristomenis;Yonekawa,Yoshihiro;Thomas,BenjaminJ;Faia,LisaJ;Chang,Emmanuel;Shulman,Julia;Olsen,KarlR;Blair,MichaelP;Shapiro,MichaelP;Ferrone,Philip;Vajzovic,Lejla;Toth,CynthiaA;Lee,ThomasC;Robinson,
通讯作者：
Robinson,
影响因子：
5.6
作者：
Golovanov, AP;Chuang, TH;Roberts, GCK
通讯作者：
Roberts, GCK
影响因子：
6.8
作者：
Geyer, M;Wittinghofer, A
通讯作者：
Wittinghofer, A