5FR2

Farnesylated RhoA-GDP in complex with RhoGDI-alpha, lysine acetylated at K178

5FR2 の概要

• エントリーDOI: 10.2210/pdb5fr2/pdb
• 関連するPDBエントリー: 5FR1
• 分子名称: TRANSFORMING PROTEIN RHOA, RHO GDP-DISSOCIATION INHIBITOR 1, FARNESYL, ... (7 entities in total)
• 機能のキーワード: signaling protein, lysine-acetylation, rhoa, ras-superfamily, rhogdi, cytoskeleton, gdp
• 由来する生物種: HOMO SAPIENS (HUMAN); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 47461.04

構造登録者

Kuhlmann, N.,Wroblowski, S.,Knyphausen, P.,de Boor, S.,Brenig, J.,Zienert, A.Y.,Meyer-Teschendorf, K.,Praefcke, G.J.K.,Nolte, H.,Krueger, M.,Schacherl, M.,Baumann, U.,James, L.C.,Chin, J.W.,Lammers, M. (登録日: 2015-12-15, 公開日: 2016-01-13, 最終更新日: 2024-10-23)

主引用文献

Kuhlmann, N.,Wroblowski, S.,Knyphausen, P.,De Boor, S.,Brenig, J.,Zienert, A.Y.,Meyer-Teschendorf, K.,Praefcke, G.J.K.,Nolte, H.,Kruger, M.,Schacherl, M.,Baumann, U.,James, L.C.,Chin, J.W.,Lammers, M.
Structural and Mechanistic Insights Into the Regulation of the Fundamental Rho-Regulator Rhogdi Alpha by Lysine Acetylation.
J.Biol.Chem., 291:5484-, 2016

PubMed Abstract: Rho proteins are small GTP/GDP-binding proteins primarily involved in cytoskeleton regulation. Their GTP/GDP cycle is often tightly connected to a membrane/cytosol cycle regulated by the Rho guanine nucleotide dissociation inhibitor α (RhoGDIα). RhoGDIα has been regarded as a housekeeping regulator essential to control homeostasis of Rho proteins. Recent proteomic screens showed that RhoGDIα is extensively lysine-acetylated. Here, we present the first comprehensive structural and mechanistic study to show how RhoGDIα function is regulated by lysine acetylation. We discover that lysine acetylation impairs Rho protein binding and increases guanine nucleotide exchange factor-catalyzed nucleotide exchange on RhoA, these two functions being prerequisites to constitute a bona fide GDI displacement factor. RhoGDIα acetylation interferes with Rho signaling, resulting in alteration of cellular filamentous actin. Finally, we discover that RhoGDIα is endogenously acetylated in mammalian cells, and we identify CBP, p300, and pCAF as RhoGDIα-acetyltransferases and Sirt2 and HDAC6 as specific deacetylases, showing the biological significance of this post-translational modification.

PubMed: 26719334
DOI: 10.1074/JBC.M115.707091

実験手法

X-RAY DIFFRACTION (3.35 Å)