Interaction of human gamma-carboxyglutamic acid domainless prothrombin with phospholipids.
The conversion of prothrombin into thrombin occurs at the surface of stimulated platelets. In order to see the influence of gamma-carboxyglutamic acid in the interaction of prothrombin with phospholipid, we investigated the direct interaction of the peptide 1-41 and prothrombin (des 1-44) with phospholipid monolayers of various compositions. Adsorption of the labeled proteins was determined by surface radioactivity measurements. Penetration of the proteins into the lipid layers was inferred from capacitance variation of the monolayer, measured by a.c. polarography. Prothrombin (des 1-44) was found both to adsorb and to penetrate the lipid monolayers, in the presence and in the absence of Ca++. The effects are higher on 100% PS than on 25% PS. This protein was also found to increase the permeability of vesicles containing 25% PS to T1+ ions, in the presence and in the absence of Ca++. Comparison with prothrombin shows that Gla residues are clearly involved in the interaction at 25% PS; nevertheless, the peptide 1-41 does not penetrate. A model of interaction of prothrombin with phospholipid, including both adsorption of prothrombin by Gla residues and its penetration by another domain, is proposed.
Lecompte
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Laboratoire d'Electrochimie Interfaciale du CNRS, Meudon, France.
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D015055:1-Carboxyglutamic Acid / Q000502:physiology; D000327:Adsorption; D002118:Calcium / Q000494:pharmacology; D002918:Chymotrypsin; D004594:Electrophysiology; D006801:Humans; D006868:Hydrolysis; D007700:Kinetics; D010446:Peptide Fragments / Q000378:metabolism*; D010539:Permeability; D010743:Phospholipids / Q000378:metabolism*; D011516:Prothrombin / Q000378:metabolism*
D010446:Peptide Fragments; D010743:Phospholipids; C059800:prothrombin (des 1-44); D015055:1-Carboxyglutamic Acid; D011516:Prothrombin; D002918:Chymotrypsin; D002118:Calcium