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Diversity and plasticity in Rab GTPase nucleotide release mechanism has consequences for Rab activation and inactivation

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Diversity and plasticity in Rab GTPase nucleotide release mechanism has consequences for Rab activation and inactivation. / Langemeyer, Lars; Nunes Bastos, Ricardo; Cai, Yiying; Itzen, Aymelt; Reinisch, Karin M; Barr, Francis A.

In: ELIFE, Vol. 3, 11.02.2014, p. e01623.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Langemeyer, L, Nunes Bastos, R, Cai, Y, Itzen, A, Reinisch, KM & Barr, FA 2014, 'Diversity and plasticity in Rab GTPase nucleotide release mechanism has consequences for Rab activation and inactivation', ELIFE, vol. 3, pp. e01623. https://doi.org/10.7554/eLife.01623

APA

Langemeyer, L., Nunes Bastos, R., Cai, Y., Itzen, A., Reinisch, K. M., & Barr, F. A. (2014). Diversity and plasticity in Rab GTPase nucleotide release mechanism has consequences for Rab activation and inactivation. ELIFE, 3, e01623. https://doi.org/10.7554/eLife.01623

Vancouver

Langemeyer L, Nunes Bastos R, Cai Y, Itzen A, Reinisch KM, Barr FA. Diversity and plasticity in Rab GTPase nucleotide release mechanism has consequences for Rab activation and inactivation. ELIFE. 2014 Feb 11;3:e01623. https://doi.org/10.7554/eLife.01623

Bibtex

@article{f4f976a99a0943ddadf0ca5539bace96,
title = "Diversity and plasticity in Rab GTPase nucleotide release mechanism has consequences for Rab activation and inactivation",
abstract = "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. ",
keywords = "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, Journal Article, Research Support, Non-U.S. Gov't",
author = "Lars Langemeyer and {Nunes Bastos}, Ricardo and Yiying Cai and Aymelt Itzen and Reinisch, {Karin M} and Barr, {Francis A}",
year = "2014",
month = feb,
day = "11",
doi = "10.7554/eLife.01623",
language = "English",
volume = "3",
pages = "e01623",
journal = "ELIFE",
issn = "2050-084X",
publisher = "eLife Sciences Publications",

}

RIS

TY - JOUR

T1 - Diversity and plasticity in Rab GTPase nucleotide release mechanism has consequences for Rab activation and inactivation

AU - Langemeyer, Lars

AU - Nunes Bastos, Ricardo

AU - Cai, Yiying

AU - Itzen, Aymelt

AU - Reinisch, Karin M

AU - Barr, Francis A

PY - 2014/2/11

Y1 - 2014/2/11

N2 - 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.

AB - 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.

KW - Adenosine Triphosphate

KW - Aspartic Acid

KW - Bacterial Proteins

KW - Catalytic Domain

KW - DNA-Binding Proteins

KW - Death Domain Receptor Signaling Adaptor Proteins

KW - Enzyme Activation

KW - Glutamine

KW - Guanine Nucleotide Exchange Factors

KW - HeLa Cells

KW - Humans

KW - Hydrolysis

KW - Listeria

KW - Models, Molecular

KW - Mutagenesis, Site-Directed

KW - Mutation

KW - Protein Conformation

KW - Signal Transduction

KW - Transfection

KW - rab GTP-Binding Proteins

KW - rab1 GTP-Binding Proteins

KW - rab5 GTP-Binding Proteins

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.7554/eLife.01623

DO - 10.7554/eLife.01623

M3 - SCORING: Journal article

C2 - 24520163

VL - 3

SP - e01623

JO - ELIFE

JF - ELIFE

SN - 2050-084X

ER -