5FR1

Double acetylated RhoGDI-alpha in complex with RhoA-GDP

5FR1 の概要

• エントリーDOI: 10.2210/pdb5fr1/pdb
• 関連するPDBエントリー: 5FR2
• 分子名称: TRANSFORMING PROTEIN RHOA, RHO GDP-DISSOCIATION INHIBITOR 1, GUANOSINE-5'-DIPHOSPHATE, ... (5 entities in total)
• 機能のキーワード: signaling protein, ras-superfamily, guanine-nucleotide-binding protein, molecular switch, actin-cytoskeleton rhogdi-alpha, nucleotide dissociation, prenylation, lysine-acetylation
• 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: 47221.21

構造登録者

Kuhlmann, N.,Wroblowski, S.,Lammers, M. (登録日: 2015-12-15, 公開日: 2016-01-13, 最終更新日: 2024-10-16)

主引用文献

Kuhlmann, N.,Wroblowski, S.,Scislowski, L.,Lammers, M.
Rhogdi Alpha Acetylation at K127 and K141 Affects Binding Towards Non-Prenylated Rhoa.
Biochemistry, 55:304-, 2016

PubMed Abstract: 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.

PubMed: 26695096
DOI: 10.1021/ACS.BIOCHEM.5B01242

実験手法

X-RAY DIFFRACTION (2.75 Å)