ArticleProceedings of the National Academy of Sciences of the United States of America2017
Multiple proteolytic events in caspase-6 self-activation impact conformations of discrete structural regions.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 32 citations in OpenAlex.
- In vivo CRISPR base editing for treatment of Huntington's disease.Nature biomedical engineering · 2026Article
- Recombinant HALT-1 induces mitochondrial-associated apoptotic mechanism in HeLa cells.Scientific reports · 2025Article
- Insights into Caspase-6 Mutations and Neuropathology in Huntington's Disease and Psychiatric Disorders: A Structural Genomics and Drug Repurposing Approach.Molecular neurobiology · 2025Article
- Article
- Caspase-14-like Proteases: An Epidermal Caspase and Its Evolutionarily Ancient Relatives.Biomolecules · 2025Review
- Radiation symptoms resemble laminopathies and the physical underlying cause may sit at the lamin A C-terminus.Molecular medicine (Cambridge, Mass.) · 2025Article
- Polyphenols fromPharmaceutics · 2025Article
- An NMR sample preparation case study: Considerations for the self-destructive protease caspase-6.PloS one · 2025Article
- Predicting the structural basis of targeted protein degradation by integrating molecular dynamics simulations with structural mass spectrometry.Nature communications · 2022Article
- Caspase-6-cleaved tau is relevant in Alzheimer's disease and marginal in four-repeat tauopathies: Diagnostic and therapeutic implications.Neuropathology and applied neurobiology · 2022Article
- Understanding the molecular role of syndecan-1 in the regulation of caspase-6 during the progression of cardiac arrhythmia.Experimental and therapeutic medicine · 2021Article
- Caspase-9 Activation of Procaspase-3 but Not Procaspase-6 Is Based on the Local Context of Cleavage Site Motifs and on Sequence.Biochemistry · 2021Article
- Entamoeba histolytica exploits the autophagy pathway in macrophages to trigger inflammation in disease pathogenesis.Mucosal immunology · 2021Article
- Exogenous Introduction of Initiator and Executioner Caspases Results in Different Apoptotic Outcomes.JACS Au · 2021Article
- Rare CASP6N73T variant associated with hippocampal volume exhibits decreased proteolytic activity, synaptic transmission defect, and neurodegeneration.Scientific reports · 2021Article
- The intricate biophysical puzzle of caspase-1 activation.Archives of biochemistry and biophysics · 2021Review
- Newly Identified Function of Caspase-6 in ZBP1-mediated Innate Immune Responses, NLRP3 Inflammasome Activation, PANoptosis, and Host Defense.Journal of cellular immunology · 2020Article
- Activation of Caspase-6 Is Promoted by a Mutant Huntingtin Fragment and Blocked by an Allosteric Inhibitor Compound.Cell chemical biology · 2019Article
- Specificity for latent C termini links the E3 ubiquitin ligase CHIP to caspases.Nature chemical biology · 2019Article
- Tri-arginine exosite patch of caspase-6 recruits substrates for hydrolysis.The Journal of biological chemistry · 2019Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Caspase-6 is critical to the neurodegenerative pathways of Alzheimer's, Huntington's, and Parkinson's diseases and has been identified as a potential molecular target for treatment of neurodegeneration. Thus, understanding the global and regional changes in dynamics and conformation provides insights into the unique properties of caspase-6 that may contribute to achieving control of its function. In this work, hydrogen/deuterium exchange MS (H/DX-MS) was used to map the local changes in the conformational flexibility of procaspase-6 at the discrete states that reflect the series of cleavage events that ultimately lead to the fully active, substrate-bound state. Intramolecular self-cleavage at Asp-193 evoked higher solvent exposure in the regions of the substrate-binding loops L1, L3, and L4 and in the 130s region, the intersubunit linker region, the 26-32 region as well as in the stabilized loop 2. Additional removal of the linker allowed caspase-6 to gain more flexibility in the 130s region and in the L2 region converting caspase-6 to a competent substrate-binding state. The prodomain region was found to be intrinsically disordered independent of the activation state of caspase-6; however, its complete removal resulted in the protection of the adjacent 26-32 region, suggesting that this region may play a regulatory role. The molecular details of caspase-6 dynamics in solution provide a comprehensive scaffold for strategic design of therapeutic approaches for neurodegenerative disorders.
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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.