Examination of the Deubiquitylation Site Selectivity of USP51 by Using Chemically Synthesized Ubiquitylated Histones
文献类型：期刊论文
| 作者 | Ai, Huasong3; Qi, Yunkun3; Guo, Jing3; Qu, Qian3; Liu, Lei3; Guo, Yu1,4; Zhao, Suwen1; Sun, Demeng2; Liu, Sanling2; Gong, Qingyue2 |
| 刊名 | CHEMBIOCHEM
 |
| 出版日期 | 2019 |
| 卷号 | 20期号:2页码:221-229 |
| 关键词 | deubiquitylation histones molecular dynamics proteins solid-phase synthesis |
| ISSN号 | 1439-4227 |
| DOI | 10.1002/cbic.201800432 |
| 文献子类 | Article |
| 英文摘要 | Histone ubiquitylation and deubiquitylation processes and the mechanisms of their regulation are closely relevant to the field of epigenetics. Recently, the deubiquitylating enzyme USP51 was reported to selectively cleave ubiquitylation on histone H2A at K13 or K15 (i.e., H2AK13Ub and H2AK15Ub), but not at K119 (i.e., H2AK119Ub), in nucleosomes in vivo. To elucidate the mechanism for the selectivity of USP51, we constructed structurally well-defined in vitro protein systems with a ubiquitin modification at precise sites. A total chemical protein synthesis procedure was developed, wherein hydrazide-based native chemical ligation was used to efficiently generate five ubiquitylated histones (H2AK13Ub, H2AK15Ub, H2AK119Ub, H2BK34Ub, and H2BK120Ub). These synthetic ubiquitylated histones were assembled into nucleosomes and subjected to in vitro USP51 deubiquitylation assays. Surprisingly, USP51 did not show preference between H2AK13/15Ub and H2AK119Ub, in contrast to previous in vivo observations. Accordingly, an understanding of the selectivity of USP51 may require consideration of other factors, such as alternative pre-existing histone modifications, competitive reader proteins, or different nucleosome quality among the in vivo extraction nucleosome and the in vitro reconstitution one. Further experiments established that USP51 in vitro could deubiquitylate a nucleosome carrying H2BK120Ub, but not H2BK34Ub. Molecular dynamics simulations suggested that USP51-catalyzed hydrolysis of ubiquitylated nucleosomes was affected by steric hindrance of the isopeptide bond. |
| 学科主题 | Biochemistry & Molecular Biology ; Pharmacology & Pharmacy |
| WOS关键词 | H2B UBIQUITYLATION ; PEPTIDE HYDRAZIDES ; STRUCTURAL BASIS ; PROTEIN ; UBIQUITINATION ; LIGATION ; CONVERGENT ; CYSTEINE ; BINDING ; DEUBIQUITINASES |
| 语种 | 英语 |
| WOS记录号 | WOS:000457615700014 |
| 出版者 | WILEY-V C H VERLAG GMBH |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/600]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所 |
| 作者单位 | 1.ShanghaiTech Univ, iHuman Inst, Sch Life Sci & Technol, Shanghai 201210, Peoples R China; 2.Univ Sci & Technol China, Sch Life Sci, Hefei 230026, Anhui, Peoples R China, 3.Tsinghua Univ, Dept Chem, MOE Key Lab Bioorgan Phosphorus Chem & Chem Biol, Tsinghua Peking Ctr Life Sci, Beijing 100084, Peoples R China; 4.Chinese Acad Sci, Shanghai Inst Nutr & Hlth, Shanghai 201210, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Ai, Huasong,Qi, Yunkun,Guo, Jing,et al. Examination of the Deubiquitylation Site Selectivity of USP51 by Using Chemically Synthesized Ubiquitylated Histones[J]. CHEMBIOCHEM,2019,20(2):221-229. |
| APA | Ai, Huasong.,Qi, Yunkun.,Guo, Jing.,Qu, Qian.,Liu, Lei.,...&,.(2019).Examination of the Deubiquitylation Site Selectivity of USP51 by Using Chemically Synthesized Ubiquitylated Histones.CHEMBIOCHEM,20(2),221-229. |
| MLA | Ai, Huasong,et al."Examination of the Deubiquitylation Site Selectivity of USP51 by Using Chemically Synthesized Ubiquitylated Histones".CHEMBIOCHEM 20.2(2019):221-229. |
入库方式： OAI收割
来源：上海营养与健康研究所
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