A Steric Gating Mechanism Dictates the Substrate Specificity of a Rab-GEF
| Autor: | J. Christopher Fromme, Solveig A. van der Vegt, Laura L. Thomas |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Steric effects
Saccharomyces cerevisiae Proteins Vesicular Transport Proteins Gating GTPase Saccharomyces cerevisiae Biology General Biochemistry Genetics and Molecular Biology Substrate Specificity 03 medical and health sciences symbols.namesake 0302 clinical medicine Humans Molecular Biology 030304 developmental biology 0303 health sciences Mechanism (biology) fungi RAB1 Cell Biology Golgi apparatus Cell biology Protein Transport rab GTP-Binding Proteins Mutation symbols Guanine nucleotide exchange factor Rab 030217 neurology & neurosurgery Developmental Biology Signal Transduction |
| Zdroj: | Developmental cell. 48(1) |
| ISSN: | 1878-1551 |
| Popis: | Summary Correct localization of Rab GTPases in cells is critical for proper function in membrane trafficking, yet the mechanisms that target Rabs to specific subcellular compartments remain controversial. Guanine nucleotide exchange factors (GEFs) activate and consequently stabilize Rab substrates on membranes, thus implicating GEFs as the primary determinants of Rab localization. A competing hypothesis is that the Rab C-terminal hypervariable domain (HVD) serves as a subcellular targeting signal. In this study, we present a unifying mechanism in which the HVD controls targeting of certain Rabs by mediating interaction with their GEFs. We demonstrate that the TRAPP complexes, two related GEFs that use the same catalytic site to activate distinct Rabs, distinguish between Ypt1 (Rab1) and Ypt31/32 (Rab11) via their divergent HVDs. Remarkably, we find that HVD length gates Rab access to the TRAPPII complex by constraining the distance between the nucleotide-binding domain and the membrane surface. |
| Databáze: | OpenAIRE |
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