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MCC950 closes the active conformation of NLRP3 to an inactive state - Nature Chemical Biology

  • ️Pelegrin, Pablo
  • ️Mon May 13 2019

Data availability

Source data for Figs. 1, 2 and 3 are presented online. Supplementary Figs. 8 and 9 present data for Figs. 1a,f,g and 3a–c,e as dot-plots to shows data distribution. Supplementary Fig. 10 presents uncropped western blots presented in the main and supplementary figures. All other data supporting the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

We thank M. C. Baños and A. I. Gómez for technical assistance with molecular biology and cell culture. We also wish to thank L. Martínez-Alarcón for help with healthy volunteer blood collection, I. Hafner-Bratkovič (National Institute of Chemistry, Ljubljana, Slovenia) for stable immortalized macrophages lines, and C. Vargas (Hospital Virgen de la Macarena, Sevilla, Spain), E. Ramos and S. Jimenez-Treviño (Hospital Central de Asturias, Oviedo, Spain), and M. Basagaña Torrento (Hospital Universitario Germans Trias i Pujol, Badalona, Spain) for samples from individuals with autoinflammatory syndromes. We also thank the patients and healthy volunteers enrolled in this study, and the Biobanco en Red de la Región de Murcia (PT13/0010/0018), which is integrated into the Spanish National Biobanks Network (B.000859), for its collaboration. This research was partially supported by the e-infrastructure program of the Research Council of Norway, and the supercomputer center of UiT at the Arctic University of Norway. The authors are also grateful for the computer resources at CTE-POWER and the technical support provided by Barcelona Supercomputing Center (RES-BCV-2018-3-0008). H.M.-B. was supported by a Rio Hortega fellowship from the Instituto Salud Carlos III (CM14/00008). D.A.-B. was supported by a Juan de la Cierva postdoctoral fellowship from the Ministerio de Economía y Competitividad (FJCI-2014-22041). This work was supported by grants from the Instituto Salud Carlos III-Fondo Europeo de Desarrollo Regional (PI13/00174 to P.P.), the Ministerio de Economia, Industria y Competitividad–Fondo Europeo de Desarrollo Regional (project nos. SAF2017-88276-R to P.P. and CTQ2017-87974-R to H.P.-S.), Fundación Séneca (20859/PI/18 to P.P.), and the European Research Council (ERC-2013-CoG 614578 to P.P.).

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Authors and Affiliations

  1. Biomedical Research Institute of Murcia (IMIB-Arrixaca), University Clinical Hospital Virgen de la Arrixaca, Murcia, Spain

    Ana Tapia-Abellán, Diego Angosto-Bazarra, Helios Martínez-Banaclocha, Carlos de Torre-Minguela & Pablo Pelegrin

  2. Bioinformatics and High Performance Computing Research Group (BIO-HPC), Computer Engineering Department, Universidad Católica de Murcia (UCAM), Murcia, Spain

    Jose P. Cerón-Carrasco & Horacio Pérez-Sánchez

  3. Department of Immunology, Hospital Clinic-IDIBAPS, Barcelona, Spain

    Juan I. Arostegui

Authors

  1. Ana Tapia-Abellán

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  2. Diego Angosto-Bazarra

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  3. Helios Martínez-Banaclocha

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  4. Carlos de Torre-Minguela

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  5. Jose P. Cerón-Carrasco

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  6. Horacio Pérez-Sánchez

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  7. Juan I. Arostegui

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  8. Pablo Pelegrin

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Contributions

A.T.-A., D.A.-B., H.M.-B. and C.dT.-M. conducted the experiments and interpreted data. J.P.C.-C. and H.P.-S. conducted BD and MD simulations. D.A.-B. performed structural modeling. J.I.A. coordinated human samples from autoinflammatory individuals. P.P. conceived, designed, and supervised this study, wrote the paper with feedback from all coauthors, and sourced funding.

Corresponding author

Correspondence to Pablo Pelegrin.

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The authors declare no competing interests.

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Tapia-Abellán, A., Angosto-Bazarra, D., Martínez-Banaclocha, H. et al. MCC950 closes the active conformation of NLRP3 to an inactive state. Nat Chem Biol 15, 560–564 (2019). https://doi.org/10.1038/s41589-019-0278-6

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  • Received: 09 July 2018

  • Accepted: 22 March 2019

  • Published: 13 May 2019

  • Issue Date: June 2019

  • DOI: https://doi.org/10.1038/s41589-019-0278-6