Universität zu Köln

Kuhlmann, Nora, Wroblowski, Sarah, Scislowski, Lukas and Lammers, Michael ORCID: 0000-0003-4168-4640 (2016). RhoGDI alpha Acetylation at K127 and K141 Affects Binding toward Nonprenylated RhoA. Biochemistry, 55 (2). S. 304 - 313. WASHINGTON: AMER CHEMICAL SOC. ISSN 0006-2960

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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 RhoGDI alpha 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 RhoGDI alpha. However, RhoGDI alpha was also shown to bind to nonprenylated Rho proteins with physiologically relevant micomolar affinities. Recently, it was discovered that RhoGDI alpha 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 RhoGDI alpha 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, RhoGDI alpha, in complex with RhoA GDP. We discover that the C-terminus of RhoA adopts a different conformation forming an intermolecular beta-sheet with the RhoGDI alpha immunoglobulin domain.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Kuhlmann, Nora UNSPECIFIED UNSPECIFIED UNSPECIFIED Wroblowski, Sarah UNSPECIFIED UNSPECIFIED UNSPECIFIED Scislowski, Lukas UNSPECIFIED UNSPECIFIED UNSPECIFIED Lammers, Michael UNSPECIFIED orcid.org/0000-0003-4168-4640 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-287129
DOI:	10.1021/acs.biochem.5b01242
Journal or Publication Title:	Biochemistry
Volume:	55
Number:	2
Page Range:	S. 304 - 313
Date:	2016
Publisher:	AMER CHEMICAL SOC
Place of Publication:	WASHINGTON
ISSN:	0006-2960
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language N-TERMINAL DOMAIN; LYSINE ACETYLATION; DISSOCIATION INHIBITORS; STRUCTURE VALIDATION; G-PROTEINS; GTPASES; PHOSPHORYLATION; COMPLEX; GERANYLGERANYLTRANSFERASE; DEGRADATION Multiple languages Biochemistry & Molecular Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/28712