TY - JOUR
T1 - Structure of TBC1D23 N-terminus reveals a novel role for rhodanese domain
AU - Liu, Dingdong
AU - Yang, Fan
AU - Liu, Zhe
AU - Wang, Jinrui
AU - Huang, Wenjie
AU - Meng, Wentong
AU - Billadeau, Daniel D.
AU - Sun, Qingxiang
AU - Mo, Xianming
AU - Jia, Da
N1 - Publisher Copyright:
© 2020 Liu et al.
PY - 2020/5/1
Y1 - 2020/5/1
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.pbio.3000746
DO - 10.1371/journal.pbio.3000746
M3 - Article
C2 - 32453802
AN - SCOPUS:85085994772
SN - 1544-9173
VL - 18
JO - PLoS biology
JF - PLoS biology
IS - 5
M1 - e3000746
ER -