ArticleThe Journal of biological chemistry2013
Histone H4 promotes prothrombin autoactivation.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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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.
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Who cites it
30 citing papers in PubMed, 69 citations in OpenAlex.
- Regulation of histones in thromboinflammation.Frontiers in immunology · 2026Review
- Sepsis-induced immunothrombosis: from cellular crosstalk to multiple organ dysfunction.Frontiers in immunology · 2026Review
- Review
- Neutrophil extracellular traps-targeting therapy with deoxyribonuclease 1 reduces large vessel occlusion-induced downstream microvascular thromboinflammation in a rat model of stroke.Research and practice in thrombosis and haemostasis · 2025Article
- Neutrophils: Linking Inflammation to Thrombosis and Unlocking New Treatment Horizons.International journal of molecular sciences · 2025Review
- Coagulation and Inflammation in COVID-19: Reciprocal Relationship between Inflammatory and Coagulation Markers.Annals of hematology · 2024Review
- Can Serum Histone H4 Level Be a Biomarker in Ulcerative Colitis?The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2024Article
- Unraveling Epigenetic Interplay between Inflammation, Thrombosis, and Immune-Related Disorders through a Network Meta-analysis.TH open : companion journal to thrombosis and haemostasis · 2024Article
- Pathophysiology of Disseminated Intravascular Coagulation in Sepsis: A Clinically Focused Overview.Cells · 2023Review
- NETs-Induced Thrombosis Impacts on Cardiovascular and Chronic Kidney Disease.Circulation research · 2023Review
- Review
- Coagulation and complement: Key innate defense participants in a seamless web.Frontiers in immunology · 2022Review
- The role of leukocytes in acute ischemic stroke-related thrombosis: a notable but neglected topic.Cellular and molecular life sciences : CMLS · 2021Review
- PEGylated nanoparticle albumin-bound steroidal ginsenoside derivatives ameliorate SARS-CoV-2-mediated hyper-inflammatory responses.Biomaterials · 2021Article
- Fibrinolysis in Platelet Thrombi.International journal of molecular sciences · 2021Review
- Circulating Histones in Sepsis: Potential Outcome Predictors and Therapeutic Targets.Frontiers in immunology · 2021Review
- Neutrophils: back in the thrombosis spotlight.Blood · 2019Review
- Biology, role and therapeutic potential of circulating histones in acute inflammatory disorders.Journal of cellular and molecular medicine · 2018Review
- Acute Traumatic Coagulopathy: The Value of Histone in Pediatric Trauma Patients.Turkish journal of haematology : official journal of Turkish Society of Haematology · 2018Article
- Structure of Coagulation Factor II: Molecular Mechanism of Thrombin Generation and Development of Next-Generation Anticoagulants.Frontiers in medicine · 2018Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Recent studies have documented the ability of prothrombin to spontaneously convert to the mature protease thrombin when Arg-320 becomes exposed to solvent for proteolytic attack upon mutation of residues in the activation domain. Whether prothrombin autoactivation occurs in the wild-type under conditions relevant to physiology remains unknown. Here, we report that binding of histone H4 to prothrombin under physiological conditions generates thrombin by autoactivation. The effect is abrogated by mutation of the catalytic Ser-525 and requires the presence of the Gla domain. Fluorescence titrations document direct binding of histone H4 to prothrombin with an affinity in the low nm range. Stopped flow data and luminescence resonance energy transfer measurements indicate that the binding mechanism obeys conformational selection. Among the two conformations of prothrombin, collapsed and fully extended, histone H4 binds selectively to the collapsed form and induces a transition toward a new conformation where the distance between Ser-101 in kringle-1 and Ser-210 in kringle-2 increases by 13 Å. These findings confirm the molecular plasticity of prothrombin emerged from recent structural studies and suggest that different conformations of the inter-kringle linker domain determine the functional behavior of prothrombin. The results also broaden our mechanistic understanding of the prothrombotic phenotype observed during cellular damage due to the release of histones in the blood stream. Prothrombin autoactivation induced by histone H4 emerges as a mechanism of pathophysiological relevance through which thrombin is generated independently of activation of the coagulation cascade.
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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.