期刊
NATURE CHEMICAL BIOLOGY
卷 6, 期 10, 页码 750-757出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/NCHEMBIO.426
关键词
-
资金
- Medical Research Council, United Kingdom
- Medical Research Council [MC_U105192732, MC_UP_A024_1008, MC_U105181009] Funding Source: researchfish
- MRC [MC_U105192732, MC_UP_A024_1008, MC_U105181009] Funding Source: UKRI
Ubiquitination is a reversible post-translational modification that regulates a myriad of eukaryotic functions. Our ability to study the effects of ubiquitination is often limited by the inaccessibility of homogeneously ubiquitinated proteins. In particular, elucidating the roles of the so-called 'atypical' ubiquitin chains (chains other than Lys48- or Lys63-linked ubiquitin), which account for a large fraction of ubiquitin polymers, is challenging because the enzymes for their biosynthesis are unknown. Here we combine genetic code expansion, intein chemistry and chemoselective ligations to synthesize 'atypical' ubiquitin chains. We solve the crystal structure of Lys6-linked diubiquitin, which is distinct from that of structurally characterized ubiquitin chains, providing a molecular basis for the different biological functions this linkage may regulate. Moreover, we profile a panel containing 10% of the known human deubiquitinases on Lys6- and Lys29-linked ubiquitin and discover that TRABID cleaves the Lys29 linkage 40-fold more efficiently than the Lys63 linkage.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据