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

Met1-specific motifs conserved in OTUB subfamily of green plants enable rice OTUB1 to hydrolyse Met1 ubiquitin chains.
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绿色植物OTUB亚家族中保守的Met1特异性基序使水稻OTUB1能够水解Met1泛素链

DOI:
10.1038/s41467-022-32364-3
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发表时间:
2022-08-09
影响因子:
16.6
通讯作者:
--
中科院分区:
综合性期刊1区
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--
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线性(MET1连接)泛素化涉及炎症和先天免疫信号。以前的研究已经确定了在哺乳动物系统中调节这种修饰的添加和移除的酶的特征。然而,针对MET1连接的泛素链的植物来源的去泛素酶只有几个报道,其作用机制仍然不清楚。在这里,我们使用一个含有脱氢丙氨酸的MET1-二泛素自杀探针,从水稻(OsOTUB1)中发现了OTUB1作为MET1连接的泛素链靶向脱泛素酶。通过求解apo OsOTUB1和OsOTUB1/MET1-二泛素复合体的晶体结构,我们发现MET1的活性是由OsOTUB1的S1‘口袋中的MET1特异基序决定的。大规模的序列比对和水解实验证明,这些基序是OTUB亚家族跨物种MET1活性的一般决定因素。对能够降解MET1连接的泛素链的OTUB的物种分布分析表明,这种活性在绿色植物中保守,在后生动物中不存在,这为原始植物和动物之间的进化分化提供了洞察力。
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 fromOryza 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.
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