Yanagitani Kota, Juszkiewicz Szymon, Hegde Ramanujan S
Medical Research Council (MRC) Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge, CB2 0QH, UK.
Science. 2017 Aug 4;357(6350):472-475. doi: 10.1126/science.aan0178.
Many nascent proteins are assembled into multiprotein complexes of defined stoichiometry. Imbalances in the synthesis of individual subunits result in orphans. How orphans are selectively eliminated to maintain protein homeostasis is poorly understood. Here, we found that the conserved ubiquitin-conjugating enzyme UBE2O directly recognized juxtaposed basic and hydrophobic patches on unassembled proteins to mediate ubiquitination without a separate ubiquitin ligase. In reticulocytes, where UBE2O is highly up-regulated, unassembled α-globin molecules that failed to assemble with β-globin were selectively ubiquitinated by UBE2O. In nonreticulocytes, ribosomal proteins that did not engage nuclear import factors were targets for UBE2O. Thus, UBE2O is a self-contained quality control factor that comprises substrate recognition and ubiquitin transfer activities within a single protein to efficiently target orphans of multiprotein complexes for degradation.
许多新生蛋白质被组装成具有确定化学计量比的多蛋白复合物。单个亚基合成的不平衡会导致产生孤儿蛋白。目前对于孤儿蛋白如何被选择性清除以维持蛋白质稳态的了解还很少。在这里，我们发现保守的泛素结合酶UBE2O能直接识别未组装蛋白质上并列的碱性和疏水区域，从而在没有单独泛素连接酶的情况下介导泛素化。在网织红细胞中，UBE2O高度上调，未能与β-珠蛋白组装的未组装α-珠蛋白分子被UBE2O选择性泛素化。在非网织红细胞中，未与核输入因子结合的核糖体蛋白是UBE2O的作用靶点。因此，UBE2O是一个独立的质量控制因子，它在单个蛋白质中兼具底物识别和泛素转移活性，能有效地将多蛋白复合物中的孤儿蛋白作为靶点进行降解。
