Davis C G, van Driel I R, Russell D W, Brown M S, Goldstein J L
J Biol Chem. 1987 Mar 25;262(9):4075-82.
The 50-residue cytoplasmic domain of the low density lipoprotein receptor (amino acids 790-839) directs the receptor to coated pits, thereby facilitating rapid endocytosis of bound low density lipoprotein. To determine the structural features required for this targeting, we produced 24 mutations in the cytoplasmic domain through use of oligonucleotide-directed mutagenesis. The first 22 amino acids of the cytoplasmic domain (residues 790-811) are sufficient for rapid internalization. The amino acid at position 807 is especially critical. Aromatic residues (tyrosine, phenylalanine, or tryptophan) at this position allow rapid internalization. Charged or uncharged aliphatic residues do not substitute. Although the requirements at the neighboring positions (806 and 808) are less stringent, the insertion of proline at position 806 is detrimental. These specificities suggest that the juxtamembranous region of the cytoplasmic domain participates in protein:protein interactions that allow the low density lipoprotein receptor to cluster in coated pits.
低密度脂蛋白受体50个氨基酸残基的胞质结构域（氨基酸790 - 839）将受体导向被膜小窝，从而促进结合的低密度脂蛋白的快速内吞作用。为了确定这种靶向作用所需的结构特征，我们通过寡核苷酸定向诱变在胞质结构域中产生了24个突变。胞质结构域的前22个氨基酸（残基790 - 811）足以实现快速内化。807位的氨基酸尤为关键。该位置的芳香族残基（酪氨酸、苯丙氨酸或色氨酸）可实现快速内化。带电荷或不带电荷的脂肪族残基不能替代。尽管相邻位置（806和808）的要求不太严格，但在806位插入脯氨酸是有害的。这些特异性表明，胞质结构域的近膜区域参与了蛋白质 - 蛋白质相互作用，使低密度脂蛋白受体能够在被膜小窝中聚集。
