A Steric Gating Mechanism Dictates the Substrate Specificity of a Rab-GEF.
GEF
GTPase
Golgi
Rab
Rab-GEF
TRAPP
trafficking
Journal
Developmental cell
ISSN: 1878-1551
Titre abrégé: Dev Cell
Pays: United States
ID NLM: 101120028
Informations de publication
Date de publication:
07 01 2019
07 01 2019
Historique:
received:
30
07
2018
revised:
23
10
2018
accepted:
07
11
2018
pubmed:
12
12
2018
medline:
2
8
2019
entrez:
12
12
2018
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 30528786
pii: S1534-5807(18)30931-6
doi: 10.1016/j.devcel.2018.11.013
pmc: PMC6324938
mid: NIHMS1512258
pii:
doi:
Substances chimiques
Saccharomyces cerevisiae Proteins
0
Vesicular Transport Proteins
0
YPT31 protein, S cerevisiae
EC 3.6.1-
YPT1 protein, S cerevisiae
EC 3.6.1.-
rab GTP-Binding Proteins
EC 3.6.5.2
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Pagination
100-114.e9Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM116942
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2018 Elsevier Inc. All rights reserved.
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