Met1-specific motifs conserved in OTUB subfamily of green plants enable rice OTUB1 to hydrolyse Met1 ubiquitin chains

• Published in: Nature communications Vol. 13; no. 1; p. 4672
• Main Authors: Lu, Lining, Zhai, Xiaoguo, Li, Xiaolong, Wang, Shuansuo, Zhang, Lijun, Wang, Luyang, Jin, Xi, Liang, Lujun, Deng, Zhiheng, Li, Zichen, Wang, Yanfeng, Fu, Xiangdong, Hu, Honggang, Wang, Jiawei, Mei, Ziqing, He, Zhengguo, Wang, Feng
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group 09.08.2022; Nature Publishing Group UK; Nature Portfolio
• Subjects: Chains; Crystal structure; Geographical distribution; Inflammation; Mammals; Plants; Ubiquitin; Ubiquitination; Viridiplantae
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-32364-3

Abstract Linear (Met1-linked) ubiquitination is involved inflammatory and innate immune signaling. Previous studies have characterized enzymes regulating the addition and removal of this modification in mammalian systems. However, only a few plant-derived deubiquitinases targeting Met1-linked ubiquitin chains have been reported and their mechanism of action remains elusive. Here, using a dehydroalanine-bearing Met1-diubiquitin suicide probe, we discover OTUB1 from Oryza sativa (OsOTUB1) as a Met1-linked ubiquitin chain-targeting deubiquitinase. By solving crystal structures of apo OsOTUB1 and an OsOTUB1/Met1-diubiquitin complex, we find that Met1 activity is conferred by Met1-specific motifs in the S1’ pocket of OsOTUB1. Large-scale sequence alignments and hydrolysis experiments provide evidence that these motifs are a general determinant of Met1 activity in the OTUB subfamily across species. Analysis of the species distribution of OTUBs capable of hydrolysing Met1-linked ubiquitin chains shows that this activity is conserved in green plants ( Viridiplantae ) and does not exist in metazoans, providing insights into the evolutionary differentiation between primitive plants and animals.