Hysteresis-like binding of coagulation factors X/Xa to procoagulant activated platelets and phospholipids results from multistep association and membrane-dependent multimerization
| Autor: | Hervé Chambost, James H. Kurasawa, Irina A. Demina, Andrey G Sarafanov, Mikhail A. Panteleev, Fazly I. Ataullakhanov, Nadezhda A. Podoplelova, Marie-Christine Alessi, Anastasia N. Sveshnikova, Sergey A. Vasil’ev |
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| Přispěvatelé: | Nutrition, obésité et risque thrombotique (NORT), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), ALESSI, Marie-Christine, Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM) |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
[SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology [SDV]Life Sciences [q-bio] Biophysics 030204 cardiovascular system & hematology Biochemistry Annexin V Membrane-dependent reaction 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Biopolymers Blood platelets Coagulation factor X Annexin Prothrombinase Humans Platelet Computer Simulation Platelet activation Binding site Phosphatidylserine Phospholipids Chemistry Vesicle Factor X [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology Cell Biology Surface Plasmon Resonance Blood coagulation Platelet Activation [SDV] Life Sciences [q-bio] 030104 developmental biology Membrane Factor Xa |
| Zdroj: | BBA-Biochimica et Biophysica Acta BBA-Biochimica et Biophysica Acta, Elsevier, 2016, 1858 (6), pp.1216-27 |
| ISSN: | 0006-3002 |
| Popis: | International audience; Binding of coagulation factors X (fX) and Xa (fXa) to activated platelets is required for the formation of membrane-dependent enzymatic complexes of intrinsic tenase and prothrombinase. We carried out an in-depth characterization of fX/fXa binding to phospholipids and gel-filtered, thrombin-activated platelets. Flow cytometry, surface plasmon resonance, and computational modeling were used to investigate interactions of fX/fXa with the membranes. Confocal microscopy was employed to study fXa binding to platelet thrombi formed in flowing whole blood under arterial conditions. Binding of fX/fXa to either vesicles or procoagulant platelets did not follow a traditional one-step reversible binding model. Their dissociation was a two-step process resulting in a plateau that was up to 10-fold greater than the saturation value observed in the association experiments. Computational modeling and experimental evidence suggested that this was caused by a combination of two-step association (mainly for fX) and multimerization on the membrane (mainly for fXa). Importantly, fX formed multimers with fXa, thereby improving its retention. The same binding/dissociation hysteresis was observed for annexin V known to form trimers on the membranes. Experiments with platelets from gray syndrome patients showed that alpha-granular factor Va provided an additional high-affinity binding site for fXa that did not affect the hysteresis. Confocal microscopy observation of fXa binding to platelet thrombi in a flow chamber and its wash-out confirmed that this phenomenon persisted under physiologically relevant conditions. This suggests its possible role of "locking" coagulation factors on the membrane and preventing their inhibition in plasma and removal from thrombi by flow. |
| Databáze: | OpenAIRE |
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