ArticleJournal of thrombosis and haemostasis : JTH2020
Fibrinogen αC-regions are not directly involved in fibrin polymerization as evidenced by a "Double-Detroit" recombinant fibrinogen mutant and knobs-mimic peptides.
Article in Journal of thrombosis and haemostasis : JTH, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 21 citations in OpenAlex.
- Fibrin as a Versatile Fibrous Biopolymer.Sub-cellular biochemistry · 2026Review
- Deconstructing fibrin(ogen) structure.Journal of thrombosis and haemostasis : JTH · 2025Review
- Fibrinogen αC-region acts as a functional safety latch: Implications for a fibrin biomechanical behaviour model.Acta biomaterialia · 2024Article
- Hyperelasticity of blood clots: Bridging the gap between microscopic and continuum scales.Journal of the mechanics and physics of solids · 2024Article
- Fungi Fibrinolytic Compound 1 Plays a Core Role in Modulating Fibrinolysis, Altering Plasma Clot Structure, and Promoting Susceptibility to Lysis.Pharmaceutics · 2023Article
- The Story of the Fibrin(ogen) αC-Domains: Evolution of Our View on Their Structure and Interactions.Thrombosis and haemostasis · 2022Review
- Article
- GPVI (Glycoprotein VI) Interaction With Fibrinogen Is Mediated by Avidity and the Fibrinogen αC-Region.Arteriosclerosis, thrombosis, and vascular biology · 2021Article
- A Fibrinogen Alpha Fragment Mitigates Chemotherapy-InducedFrontiers in oncology · 2021Article
- Fibrinogen αC-regions are not directly involved in fibrin polymerization as evidenced by a "Double-Detroit" recombinant fibrinogen mutant and knobs-mimic peptides.Journal of thrombosis and haemostasis : JTH · 2020Article
- Application of fibrin-based hydrogels for nerve protection and regeneration after spinal cord injury.Journal of biological engineering · 2020Review
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundFibrin polymerization, following fibrinopeptides A and B (FpA, FpB) cleavage, relies on newly exposed α- and β-chains N-termini (GPR, GHR; A-, B-knobs, respectively) engaging preexistent a and b pockets in other fibrin(ogen) molecules' γ- and (B)β-chains C-terminal regions. A role for mostly disordered (A)α-chains C-terminal regions "bridging" between fibrin molecules/fibrils has been proposed.
objectivesFibrinogen Detroit is a clinically observed mutation (AαR19 → S) with nonengaging GPS A-knobs. By analogy, a similar Bβ-chain mutation, BβR17 → S, should produce nonengaging GHS B-knobs. A homozygous "Double-Detroit" mutant (AαR19 → S, BβR17 → S; DD-FG) was developed: with A-a and B-b engagements endogenously blocked, other interactions would become apparent.
methodsDD-FG, wild-type recombinant (WT-FG), and human plasma (hp-FG) fibrinogen self-association was studied by turbidimetry coupled with fibrinopeptides release high-performance liquid chromatography (HPLC)/mass spectrometry analyses, and by light-scattering following size-exclusion chromatography (SE-HPLC).
resultsIn contrast to WT-FG and hp-FG, DD-FG produced no turbidity increase, irrespective of thrombin concentration. The SE-HPLC profile of concentrated DD-FG was unaffected by thrombin treatment, and light-scattering, at lower concentration, showed no intensity and hydrodynamic radius changes. Compared with hp-FG, both WT-FG and DD-FG showed no FpA cleavage difference, while ~50% FpB was not recovered. Correspondingly, SDS-PAGE/Western-blots revealed partial Bβ-chain N-terminal and Aα-chain C-terminal degradation. Nevertheless, ~70% DD-FG molecules bearing (A)αC-regions potentially able to associate were available. Higher-concentration, nearly intact hp-FG with 500-fold molar excess GPRP-NH
conclusions(A)αC-regions interactions appear too weak to assist native fibrin polymerization, at least without knobs engagement. Their role in all stages should be carefully reconsidered.
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