ArticleNature2008
Concerted multi-pronged attack by calpastatin to occlude the catalytic cleft of heterodimeric calpains.
Article in Nature, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
58 citing papers in PubMed, 142 citations in OpenAlex.
- An interbacterial cysteine protease toxin inhibits cell growth by targeting type II DNA topoisomerases GyrB and ParE.PLoS biology · 2025Article
- Structural basis of BAK sequestration by MCL-1 in apoptosis.Molecular cell · 2025Article
- Testing calpain inhibition in tumor endothelial cells: novel targetable biomarkers against glioblastoma malignancy.Frontiers in oncology · 2024Article
- Mitochondrial Autophagy in Ischemic Aged Livers.Cells · 2022Review
- Reg-1α, a New Substrate of Calpain-2 Depending on Its Glycosylation Status.International journal of molecular sciences · 2022Article
- Calpain-mediated proteolysis as driver and modulator of polyglutamine toxicity.Frontiers in molecular neuroscience · 2022Review
- Article
- The C2 domain of calpain 5 contributes to enzyme activation and membrane localization.Biochimica et biophysica acta. Molecular cell research · 2021Article
- Mechanisms Applied by Protein Inhibitors to Inhibit Cysteine Proteases.International journal of molecular sciences · 2021Review
- Calpain-2 participates in the process of calpain-1 inactivation.Bioscience reports · 2020Article
- Calpastatin Overexpression Protects against Excitotoxic Hippocampal Injury and Traumatic Spinal Cord Injury.Journal of neurotrauma · 2020Article
- p38γ MAPK contributes to left ventricular remodeling after pathologic stress and disinhibits calpain through phosphorylation of calpastatin.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Calpain 9 as a therapeutic target in TGFβ-induced mesenchymal transition and fibrosis.Science translational medicine · 2019Article
- Phasing with calcium at home.Acta crystallographica. Section F, Structural biology communications · 2019Article
- Killing Two Angry Birds with One Stone: Autophagy Activation by Inhibiting Calpains in Neurodegenerative Diseases and Beyond.BioMed research international · 2019Review
- Insertion sequence 1 from calpain-3 is functional in calpain-2 as an internal propeptide.The Journal of biological chemistry · 2018Article
- Calpain2 mediates Rab5-driven focal adhesion disassembly and cell migration.Cell adhesion & migration · 2018Article
- Unexpected role of the L-domain of calpastatin during the autoproteolytic activation of human erythrocyte calpain.Bioscience reports · 2018Article
- Structures of human calpain-3 protease core with and without bound inhibitor reveal mechanisms of calpain activation.The Journal of biological chemistry · 2018Article
- CaNature neuroscience · 2018Article
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
The Ca(2+)-dependent cysteine proteases, calpains, regulate cell migration, cell death, insulin secretion, synaptic function and muscle homeostasis. Their endogenous inhibitor, calpastatin, consists of four inhibitory repeats, each of which neutralizes an activated calpain with exquisite specificity and potency. Despite the physiological importance of this interaction, the structural basis of calpain inhibition by calpastatin is unknown. Here we report the 3.0 A structure of Ca(2+)-bound m-calpain in complex with the first calpastatin repeat, both from rat, revealing the mechanism of exclusive specificity. The structure highlights the complexity of calpain activation by Ca(2+), illustrating key residues in a peripheral domain that serve to stabilize the protease core on Ca(2+) binding. Fully activated calpain binds ten Ca(2+) atoms, resulting in several conformational changes allowing recognition by calpastatin. Calpain inhibition is mediated by the intimate contact with three critical regions of calpastatin. Two regions target the penta-EF-hand domains of calpain and the third occupies the substrate-binding cleft, projecting a loop around the active site thiol to evade proteolysis.
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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.