Structure of TBC1D23 N-terminus reveals a novel role for rhodanese domain

Liu, Dingdong and Yang, Fan and Liu, Zhe and Wang, Jinrui and Huang, Wenjie and Meng, Wentong and Billadeau, Daniel D. and Sun, Qingxiang and Mo, Xianming and Jia, Da and Walters, Kylie J. (2020) Structure of TBC1D23 N-terminus reveals a novel role for rhodanese domain. PLOS Biology, 18 (5). e3000746. ISSN 1545-7885

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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.

Item Type: Article
Subjects: Journal Eprints > Biological Science
Depositing User: Managing Editor
Date Deposited: 04 Jan 2023 06:29
Last Modified: 04 Jun 2024 10:51
URI: http://repository.journal4submission.com/id/eprint/1257

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