MCC950 directly targets the NLRP3 ATP- hydrolysis motif for inflammasome inhibition
MCC950 directly targets the NLRP3 ATP- hydrolysis motif for inflammasome inhibition
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DOI：
10.1038/s41589-019-0277-7
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发表时间：
2019-06-01
影响因子：
14.8
通讯作者：
Schroder, Kate
中科院分区：
文献类型：
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作者：
Coll, Rebecca C.;Hill, James R.;Schroder, Kate
抑制NLRP3炎性小体是开发炎症性疾病新疗法的一种很有前途的策略。MCC950是一种有效的特异性NLRP3途径的小分子抑制剂，但其分子靶点尚未确定。在这里，我们发现MCC950直接与NLRP3 NACHT结构域内的Walker B基序相互作用，从而阻断ATP水解，抑制NLRP3的激活和炎症小体的形成。
Inhibition of the NLRP3 inflammasome is a promising strategy for the development of new treatments for inflammatory diseases. MCC950 is a potent and specific small-molecule inhibitor of the NLRP3 pathway, but its molecular target is not defined. Here, we show that MCC950 directly interacts with the Walker B motif within the NLRP3 NACHT domain, thereby blocking ATP hydrolysis and inhibiting NLRP3 activation and inflammasome formation.