ArticleNature communications2021
Human RIPK3 maintains MLKL in an inactive conformation prior to 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 62 papers, 1 of them a synthesis that pooled it.
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Who cites it
62 citing papers in PubMed, 1 synthesis or guideline pooled it, 94 citations in OpenAlex.
- Comprehensive analysis of regulated cell death pathways: intrinsic disorder, protein-protein interactions, and cross-pathway communication.Apoptosis : an international journal on programmed cell death · 2025Pooled it
- Insights from integrative spatial transcriptomics in sepsis-associated acute kidney injury.Nature reviews. Nephrology · 2026Review
- Discovery of novel RIPK3 inhibitors by virtual screening and bioactivity evaluation.Molecular diversity · 2026Article
- Black Sheep: Pseudokinases Bucking the Trend to Reveal Non-Catalytic Kinase Functions.IUBMB life · 2026Review
- The kinase domain of RIPK3 tunes its scaffolding functions.Cell death and differentiation · 2026Article
- Harnessing Cuproptosis for Antitumor Immunity: A Review of Current Evidence and Therapeutic Strategies.Molecular carcinogenesis · 2026Review
- Species-specific regulation of necroptosis by STK38-dependent RIPK1 phosphorylation.Cell death and differentiation · 2026Article
- ISG15 negatively regulates RIPK3-mediated cell death and viral pathogenesis.Cell reports · 2026Article
- A conserved dimerization element is required for protein kinase activation bybioRxiv : the preprint server for biology · 2026Article
- RIPK 1 in Alzheimer's Disease: Research Progress Integrating Pathogenesis on Necroptosis-Related Neuroinflammation, and Potential Therapeutic Strategies.Biomedicines · 2026Review
- Article
- Autoinhibitory control of MLKL governs pseudokinase domain phosphorylation and oligomerization during necroptosis.Cell reports · 2026Article
- Nanoencapsulation of Tomentosin-RichPharmaceutics · 2026Article
- De novo cyclic peptides allow visualisation of the monomeric and functional amyloid conformations of the kinase RIPK3.The Biochemical journal · 2026Article
- Necroptosis in asthma: a critical driver of immune dysregulation and airway remodeling.Frontiers in immunology · 2026Review
- PANoptosis links gut dysbiosis to obstructive sleep apnea-associated atherosclerosis: a gut-vascular inflammatory axis.Frontiers in immunology · 2026Review
- Necroptosis-senescence crosstalk in tubulointerstitial fibrosis: the mtDNA-cGAS-STING-PFKFB3 axis as a metabolic bridge.Frontiers in medicine · 2026Review
- Remodeling the tumor immune microenvironment: mechanisms of crosstalk between regulated cell death macrophages.Frontiers in immunology · 2026Review
- Regulated cell death in cancer: Mechanisms, crosstalk, and opportunities for therapy.Cancer letters · 2025Review
- Decoding necrosome assembly: harmonizing signal amplification and attenuation through optimal RIP3 stoichiometry.Nature communications · 2025Article
2 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The ancestral origins of the lytic cell death mode, necroptosis, lie in host defense. However, the dysregulation of necroptosis in inflammatory diseases has led to widespread interest in targeting the pathway therapeutically. This mode of cell death is executed by the terminal effector, the MLKL pseudokinase, which is licensed to kill following phosphorylation by its upstream regulator, RIPK3 kinase. The precise molecular details underlying MLKL activation are still emerging and, intriguingly, appear to mechanistically-diverge between species. Here, we report the structure of the human RIPK3 kinase domain alone and in complex with the MLKL pseudokinase. These structures reveal how human RIPK3 structurally differs from its mouse counterpart, and how human RIPK3 maintains MLKL in an inactive conformation prior to induction of necroptosis. Residues within the RIPK3:MLKL C-lobe interface are crucial to complex assembly and necroptotic signaling in human cells, thereby rationalizing the strict species specificity governing RIPK3 activation of MLKL.
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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.