Semenza J C, Pelham H R
MRC Laboratory of Molecular Biology, Cambridge, U.K.
J Mol Biol. 1992 Mar 5;224(1):1-5. doi: 10.1016/0022-2836(92)90571-z.
Luminal proteins of the endoplasmic reticulum (ER) share a common carboxy-terminal tetrapeptide which is necessary and sufficient for their retention in the ER. In animal cells this retention signal is usually KDEL, whereas the yeast Kluyveromyces lactis uses the closely related sequences HDEL and DDEL. The yeast ERD2 gene has been shown to determine the capacity and specificity of the retention system, implying that it encodes a sorting receptor. This receptor is thought to retrieve escaped ER proteins from the Golgi, where a human homologue of this protein has been located. This dual function of binding and retrieval requires a receptor with highly specific binding at a specific location in the cell (Golgi but not ER). Here, a region of the ERD2 protein responsible for the specificity of ligand recognition has been identified using three independent approaches. A single amino acid residue is shown to selectively affect HDEL retention: substitution of residue 51 of the K. lactis receptor is sufficient to abolish recognition of HDEL but not DDEL, generating a novel retention phenotype.
内质网（ER）的腔内蛋白共享一个共同的羧基末端四肽，该四肽对于它们在内质网中的保留是必要且充分的。在动物细胞中，这种保留信号通常是KDEL，而酵母乳酸克鲁维酵母使用密切相关的序列HDEL和DDEL。酵母ERD2基因已被证明决定了保留系统的能力和特异性，这意味着它编码一种分选受体。这种受体被认为可以从高尔基体中回收逃逸的内质网蛋白，该蛋白的人类同源物已在高尔基体中定位。这种结合和回收的双重功能需要一种在细胞特定位置（高尔基体而非内质网）具有高度特异性结合的受体。在这里，使用三种独立的方法确定了ERD2蛋白中负责配体识别特异性的区域。一个单一的氨基酸残基被证明选择性地影响HDEL的保留：乳酸克鲁维酵母受体第51位残基的取代足以消除对HDEL的识别，但不会消除对DDEL的识别，从而产生一种新的保留表型。
