5FR2

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

Summary for 5FR2

• Entry DOI: 10.2210/pdb5fr2/pdb
• Related: 5FR1
• Descriptor: TRANSFORMING PROTEIN RHOA, RHO GDP-DISSOCIATION INHIBITOR 1, FARNESYL, ... (7 entities in total)
• Functional Keywords: signaling protein, lysine-acetylation, rhoa, ras-superfamily, rhogdi, cytoskeleton, gdp
• Biological source: HOMO SAPIENS (HUMAN); More
• Total number of polymer chains: 2
• Total formula weight: 47461.04

Authors

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. (deposition date: 2015-12-15, release date: 2016-01-13, Last modification date: 2024-10-23)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (3.35 Å)