Publication: MCC950 closes the active conformation of NLRP3 to an inactive state
Authors
Angosto-Bazarra, Diego ; Martínez-Banaclocha, Helios ; Torre-Minguela, Carlos de ; Cerón-Carrasco, Jose P ; Pérez-Sánchez, Horacio ; Arostegui, Juan I ; Pelegrín Vivancos, Pablo ; Tapia Abellán, Ana
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Publisher
Nature Research
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DOI
https://doi.org/10.1038/s41589-019-0278-6
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info:eu-repo/semantics/article
Description
© 2019, The Author(s), under exclusive licence to Springer Nature America, Inc. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
This document is the Accepted Manuscript version of a Published Work that appeared in final form in Nature Chemical Biology. To access the final edited and published work see https://doi.org/10.1038/s41589-019-0278-6
Abstract
NLRP3 is an innate immune sensor contributing to the development of different diseases including monogenic autoinflammatory syndromes, gout, atherosclerosis, and Alzheimer’s disease. The molecule sulfonylurea MCC950 is a NLRP3 inflammasome inhibitor with potential clinical utility. However, the mechanism of action of MCC950 remains unknown. Here, we characterize the mechanism of action of MCC950 in both wild-type and autoinflammatory-related NLRP3 mutants, demonstrating that MCC950 closes the ‘open’ conformation of active NLRP3.
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Citation
Nature Chemical Biology, 2019, Vol. 15, pp. 60-564
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