Collawn J F, Kuhn L A, Liu L F, Tainer J A, Trowbridge I S
Department of Cancer Biology, Salk Institute, San Diego, CA 92186-5800.
EMBO J. 1991 Nov;10(11):3247-53. doi: 10.1002/j.1460-2075.1991.tb04888.x.
The internalization signals of several constitutively recycling receptors have recently been identified as regions of four or six amino acids that include an aromatic residue, usually tyrosine. Here, we show that transplanted signals from the low density lipoprotein receptor (LDLR) and cation-independent mannose-6-phosphate receptor (Man-6-PR) promote rapid internalization of the transferrin receptor (TR), directly establishing that recognition signals are interchangeable, self-determined structural motifs and that signals from type I membrane proteins are active in a type II receptor. We also show that the chemical and spatial patterns of critical residues in both four- and six-residue internalization motifs are consistent with a tight turn structure. A six-residue LDLR signal is needed for activity in TR, suggesting that an amino-terminal aromatic side chain is obligatory. In contrast, the carboxy-terminal aromatic side chain in the TR signal can be replaced by a large hydrophobic residue. Thus, internalization signals apparently require an aromatic amino-terminal residue and either an aromatic or large hydrophobic carboxy-terminal residue rather than a conserved tyrosine per se. Consistent with this conclusion, predicted internalization signals from the poly-Ig receptor, YSAF, and asialoglycoprotein receptor (ASGPR) subunit H1, YQDL, also promote internalization of TR.
最近，几种组成型循环受体的内化信号已被确定为包含一个芳香族残基（通常为酪氨酸）的四个或六个氨基酸区域。在此，我们表明，来自低密度脂蛋白受体（LDLR）和不依赖阳离子的甘露糖-6-磷酸受体（Man-6-PR）的移植信号可促进转铁蛋白受体（TR）的快速内化，直接证明识别信号是可互换的、自我决定的结构基序，并且I型膜蛋白的信号在II型受体中具有活性。我们还表明，四残基和六残基内化基序中关键残基的化学和空间模式与紧密转角结构一致。TR活性需要一个六残基的LDLR信号，这表明氨基末端芳香侧链是必需的。相比之下，TR信号中的羧基末端芳香侧链可被一个大的疏水残基取代。因此，内化信号显然需要一个芳香族氨基末端残基和一个芳香族或大的疏水羧基末端残基，而不是一个保守的酪氨酸本身。与这一结论一致，来自多聚免疫球蛋白受体的预测内化信号YSAF和去唾液酸糖蛋白受体（ASGPR）亚基H1的YQDL也促进TR的内化。
