四川大学贾大等取得重要工作进展。他们研究提出，WDR11复合物是含有酸性簇货物蛋白的受体。相关研究成果2024年7月15日在线发表于《细胞》杂志上。

据介绍，囊泡运输是一个基本过程，允许将特定蛋白质（即“货物”）分类和运输到真核细胞的不同区室。货物识别主要通过供体膜上的外壳和相关蛋白质进行。然而，目前尚不清楚是否也可以在囊泡贩运的其他阶段选择货物，以进一步提高该过程的保真度。WDR11-FAM91A1复合物在网格蛋白相关AP-1复合物的下游发挥功能，促进蛋白质从内体运输到TGN。

研究人员报告了人类WDR11-FAM91A1复合物的冷冻电镜结构。WDR11直接且特异性地识别酸性簇的一个子集，称之为超酸性簇（SAC）。WDR11复合体的组装及其与含SAC蛋白的结合对于含SAC蛋白的运输和斑马鱼神经元的正常发育是不可或缺的。

总之，这一研究发现，“货物“蛋白可以在蛋白质外壳的下游以序列特异性的方式被识别。

附：英文原文

Title: The WDR11 complex is a receptor for acidic-cluster-containing cargo proteins

Author: Huaqing Deng, Guowen Jia, Ping Li, Yingying Tang, Lin Zhao, Qin Yang, Jia Zhao, Jinrui Wang, Yingfeng Tu, Xin Yong, Sitao Zhang, Xianming Mo, Daniel D. Billadeau, Zhaoming Su, Da Jia

Issue&Volume: 2024-07-15

Abstract: Vesicle trafficking is a fundamental process that allows for the sorting and transportof specific proteins (i.e., “cargoes”) to different compartments of eukaryotic cells.Cargo recognition primarily occurs through coats and the associated proteins at thedonor membrane. However, it remains unclear whether cargoes can also be selected atother stages of vesicle trafficking to further enhance the fidelity of the process.The WDR11-FAM91A1 complex functions downstream of the clathrin-associated AP-1 complexto facilitate protein transport from endosomes to the TGN. Here, we report the cryo-EMstructure of human WDR11-FAM91A1 complex. WDR11 directly and specifically recognizesa subset of acidic clusters, which we term super acidic clusters (SACs). WDR11 complexassembly and its binding to SAC-containing proteins are indispensable for the traffickingof SAC-containing proteins and proper neuronal development in zebrafish. Our studiesthus uncover that cargo proteins could be recognized in a sequence-specific mannerdownstream of a protein coat.

DOI: 10.1016/j.cell.2024.06.024

Source: https://www.cell.com/cell/abstract/S0092-8674(24)00698-6