| Autor: |
Langemeyer L; Department of Biochemistry, University of Oxford, Oxford, United Kingdom., Nunes Bastos R, Cai Y, Itzen A, Reinisch KM, Barr FA |
| Jazyk: |
angličtina |
| Zdroj: |
ELife [Elife] 2014 Feb 11; Vol. 3, pp. e01623. Date of Electronic Publication: 2014 Feb 11. |
| DOI: |
10.7554/eLife.01623 |
| Abstrakt: |
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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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