ArticleNature communications2021
Conformational interconversion of MLKL and disengagement from RIPK3 precede cell death by necroptosis.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 104 citations in OpenAlex.
- Mechanisms, regulation and clinical relevance of necroptosis.Nature reviews. Molecular cell biology · 2026Review
- The kinase domain of RIPK3 tunes its scaffolding functions.Cell death and differentiation · 2026Article
- Black Sheep: Pseudokinases Bucking the Trend to Reveal Non-Catalytic Kinase Functions.IUBMB life · 2026Review
- The role and mechanism of TNFRSF21 in promoting necroptosis of vascular endothelial cells and inducing vascular leakage in sepsis.Journal of molecular medicine (Berlin, Germany) · 2026Article
- Autoinhibitory control of MLKL governs pseudokinase domain phosphorylation and oligomerization during necroptosis.Cell reports · 2026Article
- Tissue Specific Necroptosis in the Cervix, Uterus, and Placenta in an LPS-induced Preterm Birth Model.Reproductive sciences (Thousand Oaks, Calif.) · 2026Article
- Targeting MLKL-Driven Necroptosis: A Therapeutic Target in Inflammation and Host Defense.Biomolecules · 2026Review
- Regulated cell death in organ transplantation: recent developments and mechanistic overview.Journal of molecular cell biology · 2026Review
- Extracellular vesicles from alveolar macrophages promotes pulmonary fibrosis through suppression of lung alveolar regeneration.Journal of nanobiotechnology · 2026Article
- Article
- Unconventional binding of calmodulin to CHK2 kinase inhibits catalytic activity.The Biochemical journal · 2025Article
- Necroptotic cell death consequences and disease relevance.Nature immunology · 2025Review
- Structural basis for amyloid fibril assembly by the master cell-signaling regulator receptor-interacting protein kinase 1.Nature communications · 2025Article
- Mixed Lineage Kinase Domain-Like Protein (MLKL): From Mechanisms to Therapeutic Opportunities.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- MLKL‒OPTN axis regulates herpesvirus-induced neurological sequelae.Clinical and translational medicine · 2025Article
- Targeting alveolar epithelial cells with lipid micelle-encapsulated necroptosis inhibitors to alleviate acute lung injury.Communications biology · 2025Article
- Optogenetically Activatable MLKL as a Standalone Functional Module for Necroptosis and Therapeutic Applications in Antitumoral Immunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Targeting MLKL ameliorates T-2 toxin-induced cartilage damage by inhibiting chondrocyte death and matrix degradation in mice.Archives of toxicology · 2025Article
- Lytic coelomocyte death is tuned by cleavage but not phosphorylation of MLKL in echinoderms.PLoS pathogens · 2025Article
- Inhibition of RIPK1 or RIPK3 kinase activity post ischemia-reperfusion reduces the development of chronic kidney injury.The Biochemical journal · 2025Article
4 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 4 institutions in 2 countries.
Funding
Abstract
Phosphorylation of the MLKL pseudokinase by the RIPK3 kinase leads to MLKL oligomerization, translocation to, and permeabilization of, the plasma membrane to induce necroptotic cell death. The precise choreography of MLKL activation remains incompletely understood. Here, we report Monobodies, synthetic binding proteins, that bind the pseudokinase domain of MLKL within human cells and their crystal structures in complex with the human MLKL pseudokinase domain. While Monobody-32 constitutively binds the MLKL hinge region, Monobody-27 binds MLKL via an epitope that overlaps the RIPK3 binding site and is only exposed after phosphorylated MLKL disengages from RIPK3 following necroptotic stimulation. The crystal structures identified two distinct conformations of the MLKL pseudokinase domain, supporting the idea that a conformational transition accompanies MLKL disengagement from RIPK3. These studies provide further evidence that MLKL undergoes a large conformational change upon activation, and identify MLKL disengagement from RIPK3 as a key regulatory step in the necroptosis pathway.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.