Conformational interconversion of MLKL and disengagement from RIPK3 precede cell death by necroptosis
Mixed Lineage Kinase Domain-Like (MLKL) pseudokinase is phosphorylated by RIPK3 kinase prior to cell death by necroptosis. Here, the authors use monobodies that bind to the MLKL pseudokinase domain as tools, which allowed them to determine the crystal structures of the MLKL pseudokinase domain in tw...
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2021
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oai:doaj.org-article:09c7c00c35d347a0a64667b29956b6512021-12-02T15:51:06ZConformational interconversion of MLKL and disengagement from RIPK3 precede cell death by necroptosis10.1038/s41467-021-22400-z2041-1723https://doaj.org/article/09c7c00c35d347a0a64667b29956b6512021-04-01T00:00:00Zhttps://doi.org/10.1038/s41467-021-22400-zhttps://doaj.org/toc/2041-1723Mixed Lineage Kinase Domain-Like (MLKL) pseudokinase is phosphorylated by RIPK3 kinase prior to cell death by necroptosis. Here, the authors use monobodies that bind to the MLKL pseudokinase domain as tools, which allowed them to determine the crystal structures of the MLKL pseudokinase domain in two distinct conformations. By combining their structural data with cell signalling assays and MD simulations they provide evidence that endogenous MLKL preassociates with its upstream regulator RIPK3, and that MLKL disengages from RIPK3 following the induction of necroptosis.Sarah E. GarnishYanxiang MengAkiko KoideJarrod J. SandowEric DenbaumAnnette V. JacobsenWayland YeungAndre L. SamsonChristopher R. HorneCheree FitzgibbonSamuel N. YoungPhoebe P. C. SmithAndrew I. WebbEmma J. PetrieJoanne M. HildebrandNatarajan KannanPeter E. CzabotarShohei KoideJames M. MurphyNature PortfolioarticleScienceQENNature Communications, Vol 12, Iss 1, Pp 1-14 (2021) |
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Science Q Sarah E. Garnish Yanxiang Meng Akiko Koide Jarrod J. Sandow Eric Denbaum Annette V. Jacobsen Wayland Yeung Andre L. Samson Christopher R. Horne Cheree Fitzgibbon Samuel N. Young Phoebe P. C. Smith Andrew I. Webb Emma J. Petrie Joanne M. Hildebrand Natarajan Kannan Peter E. Czabotar Shohei Koide James M. Murphy Conformational interconversion of MLKL and disengagement from RIPK3 precede cell death by necroptosis |
description |
Mixed Lineage Kinase Domain-Like (MLKL) pseudokinase is phosphorylated by RIPK3 kinase prior to cell death by necroptosis. Here, the authors use monobodies that bind to the MLKL pseudokinase domain as tools, which allowed them to determine the crystal structures of the MLKL pseudokinase domain in two distinct conformations. By combining their structural data with cell signalling assays and MD simulations they provide evidence that endogenous MLKL preassociates with its upstream regulator RIPK3, and that MLKL disengages from RIPK3 following the induction of necroptosis. |
format |
article |
author |
Sarah E. Garnish Yanxiang Meng Akiko Koide Jarrod J. Sandow Eric Denbaum Annette V. Jacobsen Wayland Yeung Andre L. Samson Christopher R. Horne Cheree Fitzgibbon Samuel N. Young Phoebe P. C. Smith Andrew I. Webb Emma J. Petrie Joanne M. Hildebrand Natarajan Kannan Peter E. Czabotar Shohei Koide James M. Murphy |
author_facet |
Sarah E. Garnish Yanxiang Meng Akiko Koide Jarrod J. Sandow Eric Denbaum Annette V. Jacobsen Wayland Yeung Andre L. Samson Christopher R. Horne Cheree Fitzgibbon Samuel N. Young Phoebe P. C. Smith Andrew I. Webb Emma J. Petrie Joanne M. Hildebrand Natarajan Kannan Peter E. Czabotar Shohei Koide James M. Murphy |
author_sort |
Sarah E. Garnish |
title |
Conformational interconversion of MLKL and disengagement from RIPK3 precede cell death by necroptosis |
title_short |
Conformational interconversion of MLKL and disengagement from RIPK3 precede cell death by necroptosis |
title_full |
Conformational interconversion of MLKL and disengagement from RIPK3 precede cell death by necroptosis |
title_fullStr |
Conformational interconversion of MLKL and disengagement from RIPK3 precede cell death by necroptosis |
title_full_unstemmed |
Conformational interconversion of MLKL and disengagement from RIPK3 precede cell death by necroptosis |
title_sort |
conformational interconversion of mlkl and disengagement from ripk3 precede cell death by necroptosis |
publisher |
Nature Portfolio |
publishDate |
2021 |
url |
https://doaj.org/article/09c7c00c35d347a0a64667b29956b651 |
work_keys_str_mv |
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