Alteration of a single hydrogen bond between class II molecules and peptide results in rapid degradation of class II molecules after invariant chain removal.
Alteration of a single hydrogen bond between class II molecules and peptide results in rapid degradation of class II molecules after invariant chain removal.
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II 类分子和肽之间的单个氢键的改变导致 II 类分子在去除不变链后快速降解。
DOI：
10.1084/jem.188.11.2139
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Sant,AJ
中科院分区：
文献类型：
--
作者：
Ceman,S;Wu,S;Jardetzky,TS;Sant,AJ
为了表征 II β 链高度保守区域的重要性，我们引入了氨基酸取代，预计该取代会消除 II 类分子和肽之间形成的氢键。我们通过基因转染在小鼠 L 细胞中表达了带有野生型 ɑ 链的突变 ß 链。突变型 II 类分子 (81ßHJ) 在内质网中正常组装并穿过高尔基复合体。当不变链 (Ii) 与 81ßHJ 共表达时，II-Ii 类复合物在内体中被降解。在 Ii 不存在的情况下，81ßHJ 的表达会导致细胞表面表达的分子对蛋白水解敏感，通过与已知与 81ßHJ 相关的肽一起孵育，可以逆转这种情况。我们认为 81ßHJ 对蛋白酶敏感，因为它无法与大多数肽有效结合，包括 II 类相关的不变链肽。该模型得到了我们的数据的支持，该数据证明了无肽野生型 IA d 分子的蛋白酶敏感性。总的来说，我们的结果表明，II 类分子和肽之间形成的氢键对于复合物的完整性和稳定性很重要，并且空 II 类分子对蛋白酶敏感并在内体中降解。 DM 的功能之一可能是确保 II 类分子连续占据凹槽。
To characterize the importance of a highly conserved region of the class II ß chain, we introduced an amino acid substitution that is predicted to eliminate a hydrogen bond formed between the class II molecule and peptide. We expressed the mutated ß chain with a wild-type ɑ chain in a murine L cell by gene transfection. The mutant class II molecule (81ßHJ) assembles normally in the endoplasmic reticulum and transits the Golgi complex. When invariant chain (Ii) is coexpressed with 81ßHJ, the class II–Ii complex is degraded in the endosomes. Expression of 81ßHJ in the absence of Ii results in a cell surface expressed molecule that is susceptible to proteolysis, a condition reversed by incubation with a peptide known to associate with 81ßHJ. We propose that 81ßHJ is protease sensitive because it is unable to productively associate with most peptides, including classII–associated invariant chain peptides. This model is supported by our data demonstrating protease sensitivity of peptide-free wild-type IA d molecules. Collectively, our results suggest both that the hydrogen bonds formed between the class II molecule and peptide are important for the integrity and stability of the complex, and that empty class II molecules are protease sensitive and degraded in endosomes. One function of DM may be to insure continuous groove occupancy of the class II molecule.