
Structure of TBC1D23 N-terminus reveals a novel role for rhodanese domain
Author(s) -
Dingdong Liu,
Fan Yang,
Zhe Liu,
Jinrui Wang,
Wenjie Huang,
Meng Wei,
Daniel D. Billadeau,
Qingxiang Sun,
Xianming Mo,
Da Jia
Publication year - 2020
Publication title -
plos biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.127
H-Index - 271
eISSN - 1545-7885
pISSN - 1544-9173
DOI - 10.1371/journal.pbio.3000746
Subject(s) - biology , endosome , rhodanese , golgi apparatus , microbiology and biotechnology , vesicular transport proteins , sulfurtransferase , transport protein , organelle , zebrafish , adp ribosylation factor , gtpase , allosteric regulation , phosphatase , rab , endoplasmic reticulum , biochemistry , phosphorylation , enzyme , vacuolar protein sorting , cysteine , gene , intracellular
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 (D23 N ), 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.