Locking GTPases covalently in their functional states

David Wiegandt, Sophie Vieweg, Frank Hofmann, Daniel Koch, Fu Li, Yao-Wen Wu, Aymelt Itzen, Matthias P. Müller and Roger S. Goody ()
Additional contact information
David Wiegandt: Max Planck Institute of Molecular Physiology
Sophie Vieweg: Max Planck Institute of Molecular Physiology
Frank Hofmann: Max Planck Institute of Molecular Physiology
Daniel Koch: Max Planck Institute of Molecular Physiology
Fu Li: Max Planck Institute of Molecular Physiology
Yao-Wen Wu: Max Planck Institute of Molecular Physiology
Aymelt Itzen: Center for Integrated Protein Science Munich (CIPSM), Technische Universität München
Matthias P. Müller: Max Planck Institute of Molecular Physiology
Roger S. Goody: Max Planck Institute of Molecular Physiology

Nature Communications, 2015, vol. 6, issue 1, 1-10

Abstract: Abstract GTPases act as key regulators of many cellular processes by switching between active (GTP-bound) and inactive (GDP-bound) states. In many cases, understanding their mode of action has been aided by artificially stabilizing one of these states either by designing mutant proteins or by complexation with non-hydrolysable GTP analogues. Because of inherent disadvantages in these approaches, we have developed acryl-bearing GTP and GDP derivatives that can be covalently linked with strategically placed cysteines within the GTPase of interest. Binding studies with GTPase-interacting proteins and X-ray crystallography analysis demonstrate that the molecular properties of the covalent GTPase–acryl–nucleotide adducts are a faithful reflection of those of the corresponding native states and are advantageously permanently locked in a defined nucleotide (that is active or inactive) state. In a first application, in vivo experiments using covalently locked Rab5 variants provide new insights into the mechanism of correct intracellular localization of Rab proteins.

Date: 2015
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms8773 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8773

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms8773

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().