Oligomeric states of ASC specks regulate inflammatory responses by inflammasome in the extracellular space.
Oligomeric states of ASC specks regulate inflammatory responses by inflammasome in the extracellular space.
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DOI：
10.1038/s41420-023-01438-6
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发表时间：
2023-04-29
影响因子：
7
通讯作者：
Kim, Hak-Sung
中科院分区：
文献类型：
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作者：
Yu, Tae-Geun;Cha, Jeong Seok;Kim, Gijeong;Sohn, Yoo-Kyoung;Yoo, Youngki;Kim, Uijin;Song, Ji-Joon;Cho, Hyun-Soo;Kim, Hak-Sung
炎性小体是一种多蛋白复合物，在宿主防御病原体中起着至关重要的作用。已知通过炎性小体的下游炎症反应与ASC斑点的寡聚化程度相关，但详细机制仍未探索。在这里，我们证明了ASC斑点的寡聚化程度调节细胞外空间中的caspase-1激活。开发了一种对ASC的pyrin结构域（PYD）具有特异性的蛋白结合剂（ASCPYD），结构分析表明该蛋白结合剂有效抑制PYD之间的相互作用，将ASC斑点分解为低聚状态。具有低寡聚化程度的ASC斑点显示出通过caspase-1的CARD（caspase-1CARD）和ASC的CARD（ASCCARD）之间的相互作用招募和加工更多的过早caspase-1来增强caspase-1的活化。这些发现可以为控制炎性小体介导的炎症过程以及开发炎性小体靶向药物提供见解。
Inflammasomes are multi-protein complexes and play a crucial role in host defense against pathogens. Downstream inflammatory responses through inflammasomes are known to be related to the oligomerization degree of ASC specks, but the detailed mechanism still remains unexplored. Here, we demonstrate that oligomerization degrees of ASC specks regulate the caspase-1 activation in the extracellular space. A protein binder specific for a pyrin domain (PYD) of ASC (ASCPYD) was developed, and structural analysis revealed that the protein binder effectively inhibits the interaction between PYDs, disassembling ASC specks into low oligomeric states. ASC specks with a low oligomerization degree were shown to enhance the activation of caspase-1 by recruiting and processing more premature caspase-1 through interactions between CARD of caspase-1 (caspase-1CARD) and CARD of ASC (ASCCARD). These findings can provide insight into controlling the inflammasome-mediated inflammatory process as well as the development of inflammasome-targeting drugs.
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影响因子：
7.3
作者：
Nagar A;Rahman T;Harton JA
通讯作者：
Harton JA
DOI：
10.3233/jad-179941
发表时间：
2018
期刊：
Journal of Alzheimer's disease : JAD
影响因子：
--
作者：
Cline EN;Bicca MA;Viola KL;Klein WL
通讯作者：
Klein WL
影响因子：
16
作者：
Martinon, F;Burns, K;Tschopp, J
通讯作者：
Tschopp, J
影响因子：
30.5
作者：
Baroja-Mazo, Alberto;Martin-Sanchez, Fatima;Pelegrin, Pablo
通讯作者：
Pelegrin, Pablo
适配器 ASC 具有传播炎症的细胞外活性和“prionoid”活性。
影响因子：
30.5
作者：
通讯作者：
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