The molecular mechanism and evolutionary divergence of caspase 3/7-regulated gasdermin E activation
文献类型：期刊论文
| 作者 | Xu, Hang1,2,3,4 ; Yuan, Zihao2,3,4; Qin, Kunpeng1,2,3,4; Jiang, Shuai1,2,3,4; Sun, Li1,2,3,4
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| 刊名 | ELIFE
 |
| 出版日期 | 2024-03-15 |
| 卷号 | 12页码:21 |
| 关键词 | pufferfish gasdermin E caspase 3 pyroptosis caspase 7 evolution Other |
| ISSN号 | 2050-084X |
| DOI | 10.7554/eLife.89974 |
| 通讯作者 | Jiang, Shuai(sjiang@qdio.ac.cn) ; Sun, Li(lsun@qdio.ac.cn) |
| 英文摘要 | Caspase (CASP) is a family of proteases involved in cleavage and activation of gasdermin, the executor of pyroptosis. In humans, CASP3 and CASP7 recognize the same consensus motif DxxD, which is present in gasdermin E (GSDME). However, human GSDME is cleaved by CASP3 but not by CASP7. The underlying mechanism of this observation is unclear. In this study, we identified a pyroptotic pufferfish GSDME that was cleaved by both pufferfish CASP3/7 and human CASP3/7. Domain swapping between pufferfish and human CASP and GSDME showed that the GSDME C-terminus and the CASP7 p10 subunit determined the cleavability of GSDME by CASP7. p10 contains a key residue that governs CASP7 substrate discrimination. This key residue is highly conserved in vertebrate CASP3 and in most vertebrate (except mammalian) CASP7. In mammals, the key residue is conserved in non-primates (e.g., mouse) but not in primates. However, mouse CASP7 cleaved human GSDME but not mouse GSDME. These findings revealed the molecular mechanism of CASP7 substrate discrimination and the divergence of CASP3/7-mediated GSDME activation in vertebrate. These results also suggested that mutation-mediated functional alteration of CASP probably enabled the divergence and specialization of different CASP members in the regulation of complex cellular activities in mammals. |
| WOS关键词 | STRUCTURAL BASIS ; CELL-DEATH ; PYROPTOSIS ; INFLAMMASOME ; INHIBITION ; CLEAVAGE ; DISTINCT ; GSDMD ; FAMILY ; ROLES |
| 资助项目 | Science and Technology Innovation Project of Laoshan Laboratory[LSKJ202203000] ; Science & Technology Innovation Project of Laoshan Laboratory[2021204] ; Youth Innovation Promotion Association CAS[41876175] ; National Natural Science Foundation of China[2018] ; National Natural Science Foundation of China[2021] ; Taishan Scholar Program of Shandong Province |
| WOS研究方向 | Life Sciences & Biomedicine - Other Topics |
| 语种 | 英语 |
| WOS记录号 | WOS:001185971100001 |
| 出版者 | eLIFE SCIENCES PUBL LTD |
| 源URL | [http://ir.qdio.ac.cn/handle/337002/184828]  |
| 专题 | 海洋研究所_实验海洋生物学重点实验室 |
| 通讯作者 | Jiang, Shuai; Sun, Li |
| 作者单位 | 1.Univ Chinese Acad Sci, Coll Marine Sci, Qingdao, Peoples R China 2.Qingdao Marine Sci & Technol Ctr, Lab Marine Biol & Biotechnol, Qingdao, Peoples R China 3.Chinese Acad Sci, CAS Ctr Ocean Mega Sci, Qingdao, Peoples R China 4.Inst Oceanol, Chinese Acad Sci, CAS & Shandong Prov Key Lab Expt Marine Biol, Qingdao, Peoples R China |
| 推荐引用方式 GB/T 7714 | Xu, Hang,Yuan, Zihao,Qin, Kunpeng,et al. The molecular mechanism and evolutionary divergence of caspase 3/7-regulated gasdermin E activation[J]. ELIFE,2024,12:21. |
| APA | Xu, Hang,Yuan, Zihao,Qin, Kunpeng,Jiang, Shuai,&Sun, Li.(2024).The molecular mechanism and evolutionary divergence of caspase 3/7-regulated gasdermin E activation.ELIFE,12,21. |
| MLA | Xu, Hang,et al."The molecular mechanism and evolutionary divergence of caspase 3/7-regulated gasdermin E activation".ELIFE 12(2024):21. |
入库方式： OAI收割
来源：海洋研究所
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