Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

Ras superfamily GTPase activation and inactivation occur by canonical nucleotide exchange and GTP hydrolysis mechanisms. Despite conservation of active-site residues, the Ras-related Rab GTPase activation pathway differs from Ras and between different Rabs. Analysis of DENND1-Rab35, Rabex-Rab5, TRAPP-Rab1 and DrrA-Rab1 suggests Rabs have the potential for activation by distinct GDP-release pathways. Conserved active-site residues in the Rab switch II region stabilising the nucleotide-free form differentiate these pathways. For DENND1-Rab35 and DrrA-Rab1 the Rab active-site glutamine, often mutated to create constitutively active forms, is involved in GEF mediated GDP-release. By contrast, in Rab5 the switch II aspartate is required for Rabex mediated GDP-release. Furthermore, Rab1 switch II glutamine mutants refractory to activation by DrrA can be activated by TRAPP, showing that a single Rab can be activated by more than one mechanistically distinct GDP-release pathway. These findings highlight plasticity in the activation mechanisms of closely related Rab GTPases. DOI: http://dx.doi.org/10.7554/eLife.01623.001.

Original publication

DOI

10.7554/eLife.01623

Type

Journal article

Journal

Elife

Publication Date

11/02/2014

Volume

3

Keywords

Rab GTPase, membrane traffic, nucleotide exchange factor, Adenosine Triphosphate, Aspartic Acid, Bacterial Proteins, Catalytic Domain, DNA-Binding Proteins, Death Domain Receptor Signaling Adaptor Proteins, Enzyme Activation, Glutamine, Guanine Nucleotide Exchange Factors, HeLa Cells, Humans, Hydrolysis, Listeria, Models, Molecular, Mutagenesis, Site-Directed, Mutation, Protein Conformation, Signal Transduction, Transfection, rab GTP-Binding Proteins, rab1 GTP-Binding Proteins, rab5 GTP-Binding Proteins