The medium subunits of adaptor complexes recognize distinct but overlapping sets of tyrosine-based sorting signals
The medium subunits of adaptor complexes recognize distinct but overlapping sets of tyrosine-based sorting signals
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DOI：
10.1074/jbc.273.40.25915
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发表时间：
1998-10-02
影响因子：
4.8
通讯作者：
Bonifacino, JS
中科院分区：
文献类型：
--
作者：
Ohno, H;Aguilar, RC;Bonifacino, JS
符合基序 YXXO（Y 是酪氨酸，X 是任何氨基酸，O 是具有庞大疏水侧链的氨基酸（亮氨酸、异亮氨酸、苯丙氨酸、蛋氨酸、缬氨酸））的基于酪氨酸的分选信号与网格蛋白接头 (AP) 复合物的中 (mu) 亚基相互作用。我们通过使用酵母双杂交系统筛选组合 XYXYXXO 文库，分析了 YXXO 信号分别与 AP-1、AP-2 和 AP-3 复合物的 mu 1、mu 2 和 mu 3（A 或 B）亚基之间相互作用的选择性。发现所有中等亚基都偏爱位置 Y+2 处的脯氨酸，这表明 YXXO 信号通过多肽主链的弯曲而稳定。除了这种共同偏好之外，每个中等亚基都偏爱 X 和 O 位点上的特定残基组；这些偏好与不同接头复合物在快速内吞作用和溶酶体靶向中的拟议作用一致。这些分析还揭示了相当大的特异性重叠，这表明其他因素（例如信号背景）必定是识别的重要决定因素。
Tyrosine-based sorting signals conforming to the motif YXXO (Y is tyrosine, X is any amino acid, and O is an amino acid with a bulky hydrophobic side chain (leucine, isoleucine, phenylalanine, methionine, valine)) interact with the medium (mu) subunits of clathrin adaptor (AP) complexes. We have analyzed the selectivity of interaction between YXXO signals and the mu 1, mu 2, and mu 3 (A or B) subunits of the AP-1, AP-2, and AP-3 complexes, respectively, by screening a combinatorial XYXYXXO library using the yeast two-hybrid system. All the medium subunits were found to prefer proline at position Y+2, suggesting that YXXO signals are stabilized by a bend in the polypeptide backbone. Other than for this common preference, each medium subunit favored specific sets of residues at the X and O positions; these preferences were consistent with the proposed roles of the different adaptor complexes in rapid endocytosis and lysosomal targeting. A considerable specificity overlap was also revealed by these analyses, suggesting that additional factors, such as the context of the signals, must be important determinants of recognition.