Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
Institute of Medical Microbiology, University of Zurich, 8006 Zurich, Switzerland.
Science. 2019 Mar 8;363(6431):1103-1107. doi: 10.1126/science.aaw2859.
Selective export and retrieval of proteins between the endoplasmic reticulum (ER) and Golgi apparatus is indispensable for eukaryotic cell function. An essential step in the retrieval of ER luminal proteins from the Golgi is the pH-dependent recognition of a carboxyl-terminal Lys-Asp-Glu-Leu (KDEL) signal by the KDEL receptor. Here, we present crystal structures of the chicken KDEL receptor in the apo ER state, KDEL-bound Golgi state, and in complex with an antagonistic synthetic nanobody (sybody). These structures show a transporter-like architecture that undergoes conformational changes upon KDEL binding and reveal a pH-dependent interaction network crucial for recognition of the carboxyl terminus of the KDEL signal. Complementary in vitro binding and in vivo cell localization data explain how these features create a pH-dependent retrieval system in the secretory pathway.
内质网（ER）和高尔基体之间蛋白质的选择性输出和回收对真核细胞功能至关重要。从高尔基体中回收内质网腔蛋白的一个重要步骤是，KDEL 受体依赖于 pH 值识别羧基末端赖氨酸-天冬氨酸-谷氨酸-亮氨酸（KDEL）信号。在这里，我们展示了鸡 KDEL 受体在apo ER 状态、KDEL 结合的高尔基体状态以及与拮抗合成纳米体（sybody）复合物的晶体结构。这些结构显示了一种转运蛋白样的结构，在 KDEL 结合时发生构象变化，并揭示了一个对 KDEL 信号羧基末端识别至关重要的 pH 依赖性相互作用网络。体外结合和体内细胞定位数据的补充解释了这些特征如何在分泌途径中创建一个 pH 依赖性的回收系统。
