Structural basis for pH-dependent retrieval of ER proteins from the Golgi by the KDEL receptor
Structural basis for pH-dependent retrieval of ER proteins from the Golgi by the KDEL receptor
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DOI：
10.1126/science.aaw2859
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发表时间：
2019-03-08
期刊：
影响因子：
56.9
通讯作者：
Newstead, Simon
中科院分区：
文献类型：
--
作者：
Brauer, Philipp;Parker, Joanne L.;Newstead, Simon
蛋白质在内质网和高尔基体之间的选择性输出和检索是真核细胞功能不可缺少的。从高尔基体中获取内质网蛋白的一个重要步骤是KDEL受体对羧基端Lys-Asp-Glu-Leu （KDEL）信号的ph依赖性识别。在这里，我们展示了鸡KDEL受体在载脂蛋白ER状态、KDEL结合高尔基态以及与拮抗合成纳米体（sybody）复合物下的晶体结构。这些结构显示了一种转运蛋白样结构，在KDEL结合时发生构象变化，并揭示了一个ph依赖的相互作用网络，这对于识别KDEL信号的羧基端至关重要。互补的体外结合和体内细胞定位数据解释了这些特征如何在分泌途径中创建ph依赖的检索系统。
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.