PUBLICATION
Structure of TBC1D23 N-terminus reveals a novel role for rhodanese domain
- Authors
- Liu, D., Yang, F., Liu, Z., Wang, J., Huang, W., Meng, W., Billadeau, D.D., Sun, Q., Mo, X., Jia, D.
- ID
- ZDB-PUB-200527-5
- Date
- 2020
- Source
- PLoS Biology 18: e3000746 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- ADP-Ribosylation Factors/metabolism
- Animals
- Autoantigens/metabolism*
- Brain/embryology*
- Escherichia coli
- GTPase-Activating Proteins/chemistry
- GTPase-Activating Proteins/isolation & purification
- GTPase-Activating Proteins/metabolism*
- Golgi Matrix Proteins/metabolism*
- HEK293 Cells
- HeLa Cells
- Humans
- Membrane Proteins/metabolism
- Protein Conformation
- Protein Domains
- Thiosulfate Sulfurtransferase/metabolism*
- Zebrafish
- PubMed
- 32453802 Full text @ PLoS Biol.
Citation
Liu, D., Yang, F., Liu, Z., Wang, J., Huang, W., Meng, W., Billadeau, D.D., Sun, Q., Mo, X., Jia, D. (2020) Structure of TBC1D23 N-terminus reveals a novel role for rhodanese domain. PLoS Biology. 18:e3000746.
Abstract
Members of the Tre2-Bub2-Cdc16 (TBC) family often function to regulate membrane trafficking and to control signaling transductions pathways. As a member of the TBC family, TBC1D23 is critical for endosome-to-Golgi cargo trafficking by serving as a bridge between Golgi-bound golgin-97/245 and the WASH/FAM21 complex on endosomal vesicles. However, the exact mechanisms by which TBC1D23 regulates cargo transport are poorly understood. Here, we present the crystal structure of the N-terminus of TBC1D23 (D23N), which consists of both the TBC and rhodanese domains. We show that the rhodanese domain is unlikely to be an active sulfurtransferase or phosphatase, despite containing a putative catalytic site. Instead, it packs against the TBC domain and forms part of the platform to interact with golgin-97/245. Using the zebrafish model, we show that impacting golgin-97/245-binding, but not the putative catalytic site, impairs neuronal growth and brain development. Altogether, our studies provide structural and functional insights into an essential protein that is required for organelle-specific trafficking and brain development.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping