Chemical Synthesis of diSUMO Photoaffinity Probes for the Identification of PolySUMO Chain-Specific Interacting Proteins

Chemical Synthesis of diSUMO Photoaffinity Probes for the Identification of PolySUMO Chain-Specific Interacting Proteins
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用于鉴定 PolySUMO 链特异性相互作用蛋白的 diSUMO 光亲和探针的化学合成

DOI:
10.31635/ccschem.020.202000282
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发表时间:
2021-04
期刊:
影响因子:
11.2
通讯作者:
Li Yiming
Li Yiming
中科院分区:
--
文献类型:
--
作者:
Wang Yu;Chen Chenchen;Meng Xianbin;Fan Jian;Pan Man;Chen Jingnan;Deng Haiteng;Shi Jing;Liu Lei;Li Yiming

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小泛素样修饰剂(sumo)是一种可以形成聚合链的蛋白质修饰剂。它们是细胞过程中的重要信号,它们的研究和分析需要分子工具的发展。在此,作者报道了一种高效的化学蛋白质合成方法,通过连接四种容易合成的肽,生成基于sumo -2的二聚体光亲和探针。在HeLa细胞核裂解液上使用diSUMO-2探针进行蛋白质组学研究发现,与monoSUMO探针相比,它可以捕获明显不同的蛋白质选择。这导致鉴定出一些以前未知的SUMO链特异性相互作用蛋白,如40S核糖体蛋白S3,其对多SUMO链的亲和力明显高于单体SUMO。总之,这些结果强调了在其他物种中开发基于SUMO链的探针的必要性,并揭示了多sumoylation在疾病中的重要作用。
Small ubiquitin-like modifiers (SUMOs) are protein modifiers that can form polymeric chains. They are important signals in cellular processes, and their study and profiling require the development of molecular tools. Herein, the authors have reported an efficient chemical protein synthesis approach for the generation of dimeric SUMO-2-based photoaffinity probes through the ligation of four readily synthesizable peptides. Proteomic studies using this diSUMO-2 probe on HeLa cell nuclear lysate found it to capture a significantly different selection of proteins compared with its monoSUMO counterparts. This resulted in the identification of several previously unknown SUMO chain-specific interacting proteins such as 40S ribosomal protein S3, which showed a significantly higher affinity for polySUMO chains than monomeric SUMO. Collectively, these results emphasize the need to develop SUMO chain-based probes in other species, and to shed light on the important role of polySUMOylation in diseases.