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Updated: Aug 13, 2026

Preparation of Nucleosome Core Particles Complexed with DNA Repair Factors for Cryo-Electron Microscopy Structural Determination
Published on: August 17, 2022
Cryo-EM structure of the WDR11-FAM91A1-C17orf75 complex involved in retrograde trafficking
Yifan Zhang1, Zhimin Liu2, Ziyue Chen1
1State Key Laboratory of RNA Innovation, Science and Engineering, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China.
None:
Retrograde trafficking from endosomes to trans-Golgi network is essential for cellular homeostasis. While the WDR11-FAM91A1-C17orf75 (WFC) complex facilitates this process, its structural organization and the role of C17orf75 remain unclear. Here, we present cryo-EM structures of human WFC complex in monomeric and dimeric forms at 3.34 Å and 3.07 Å resolution, respectively. The WFC complex forms a dimer through the α-solenoid domains of WDR11. FAM91A1 serves as a central scaffold that interacts directly with both WDR11 and C17orf75, whereas WDR11 and C17orf75 have no direct contact. C17orf75 features an N-terminal longin-like domain and a C-terminal DENN-like domain and contains a positively charged groove that may cooperate with WDR11 in recognizing acidic-cluster-containing cargo proteins. Functional analyses demonstrate that C17orf75 is indispensable for the proper intracellular localization of the acidic-cluster-containing cargo proteins CI-MPR, KIAA0319L, and VAMP4. These findings establish C17orf75 as an integral component of the WFC complex in endosome-to-TGN trafficking.
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