Department of Biochemistry, University of Oxford, South Parks Rd, Oxford OX1 3QU, UK
J Cell Sci. 2020 Oct 9;133(19):jcs250100. doi: 10.1242/jcs.250100.
Protein localisation in the cell is controlled through the function of trafficking receptors, which recognise specific signal sequences and direct cargo proteins to different locations. The KDEL receptor (KDELR) was one of the first intracellular trafficking receptors identified and plays an essential role in maintaining the integrity of the early secretory pathway. The receptor recognises variants of a canonical C-terminal Lys-Asp-Glu-Leu (KDEL) signal sequence on ER-resident proteins when these escape to the Golgi, and targets these proteins to COPI- coated vesicles for retrograde transport back to the ER. The empty receptor is then recycled from the ER back to the Golgi by COPII-coated vesicles. Crystal structures of the KDELR show that it is structurally related to the PQ-loop family of transporters that are found in both pro- and eukaryotes, and shuttle sugars, amino acids and vitamins across cellular membranes. Furthermore, analogous to PQ-loop transporters, the KDELR undergoes a pH-dependent and ligand-regulated conformational cycle. Here, we propose that the striking structural similarity between the KDELR and PQ-loop transporters reveals a connection between transport and trafficking in the cell, with important implications for understanding trafficking receptor evolution and function.
蛋白质在细胞中的定位是通过转运受体的功能来控制的，转运受体识别特定的信号序列，并将货物蛋白导向不同的位置。KDEL 受体（KDELR）是最早被鉴定的细胞内转运受体之一，在维持早期分泌途径的完整性方面发挥着重要作用。当内质网驻留蛋白逃逸到高尔基体时，受体识别 ER 驻留蛋白上的经典 C 端赖氨酸-天冬氨酸-谷氨酸-亮氨酸（KDEL）信号序列的变体，并将这些蛋白靶向 COPI- 被膜小泡进行逆行运输回到内质网。然后，空受体通过 COPII 被膜小泡从内质网回收到高尔基体。KDELR 的晶体结构表明，它在结构上与 PQ-环家族转运体有关，这些转运体存在于原核生物和真核生物中，并在细胞膜之间穿梭运输糖、氨基酸和维生素。此外，与 PQ-环转运体类似，KDELR 经历 pH 依赖性和配体调节的构象循环。在这里，我们提出，KDELR 和 PQ-环转运体之间惊人的结构相似性揭示了细胞内运输和转运之间的联系，这对理解转运受体的进化和功能具有重要意义。
