A Polypeptide Region of Bovine Prothrombin Specific for Binding to Phospholipids

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1973 May 1

PMID 4514304

Citations 20

Authors

S N Gitel

W G Owen

C T Esmon

C M Jackson

Affiliations

Soon will be listed here.

Abstract

The blood-clotting protein prothrombin can be converted to thrombin in free solution by the proteolytic enzyme, activated factor X. When prothrombin is bound to the surface of phospholipid vesicles, the rate of thrombin generation is increased more than 30-fold over the rate of unbound prothrombin. If the prothrombin activation process is terminated after a time interval in which less than 10% of the expected thrombin has been produced, two major products are found in the activation mixture. These products have been termed intermediate 1, a precursor of thrombin, and fragment 1. The conversion of intermediate 1 to thrombin is not accelerated by phospholipid nor can binding of this intermediate to phospholipid particles be demonstrated. In contrast, fragment 1, the other activation product derived from prothrombin, binds to phospholipid particles under the same conditions as prothrombin. On the basis of these observations, we propose that the prothrombin molecule contains a specific region of polypeptide chain for binding to phospholipid particles. This specific polypeptide region or lipid interaction site is part of the nonthrombin-forming activation fragment.

Citing Articles

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References

Stenn K, BLOUT E . Mechanism of bovine prothrombin activation by an insoluble preparation of bovine factor X a (thrombokinase). Biochemistry. 1972; 11(24):4502-15. DOI: 10.1021/bi00774a012. View

Hemker H, Muller A, Loeliger E . Two types of prothrombin in vitamin K deficiency. Thromb Diath Haemorrh. 1970; 23(3):633-7. View

Laemmli U . Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970; 227(5259):680-5. DOI: 10.1038/227680a0. View

Troll W, CANNAN R . A modified photometric ninhydrin method for the analysis of amino and imino acids. J Biol Chem. 1953; 200(2):803-11. View

LOCHANG T, Sweeley C . CHARACTERIZATION OF LIPIDS FROM CANINE ADRENAL GLANDS. Biochemistry. 1963; 2:592-604. DOI: 10.1021/bi00903a036. View

Cubero Robles E, van den Berg D . Synthesis of lecithins by acylation of O-(sn-glycero-3-phosphoryl) choline with fatty acid anhydrides. Biochim Biophys Acta. 1969; 187(4):520-6. DOI: 10.1016/0005-2760(69)90049-6. View

Stenflo J, Ganrot P . Vitamin K and the biosynthesis of prothrombin. I. Identification and purification of a dicoumarol-induced abnormal prothrombin from bovine plasma. J Biol Chem. 1972; 247(24):8160-6. View

Jobin F, Esnouf M . Studies on the formation of the prothrombin-converting complex. Biochem J. 1967; 102(3):666-74. PMC: 1270313. DOI: 10.1042/bj1020666. View

BARTLETT G . Phosphorus assay in column chromatography. J Biol Chem. 1959; 234(3):466-8. View

10.

Hauser H . The effect of ultrasonic irradiation on the chemical structure of egg lecithin. Biochem Biophys Res Commun. 1971; 45(4):1049-55. DOI: 10.1016/0006-291x(71)90443-8. View

11.

Yang S, Freer S, Benson A . Transphosphatidylation by phospholipase D. J Biol Chem. 1967; 242(3):477-84. View

12.

Davis B . DISC ELECTROPHORESIS. II. METHOD AND APPLICATION TO HUMAN SERUM PROTEINS. Ann N Y Acad Sci. 1964; 121:404-27. DOI: 10.1111/j.1749-6632.1964.tb14213.x. View

13.

Denson K . Coagulant and anticoagulant action of snake venoms. Toxicon. 1969; 7(1):5-11. DOI: 10.1016/0041-0101(69)90154-8. View

14.

Papahadjopoulos D, HANAHAN D . OBSERVATIONS ON THE INTERACTION OF PHOSPHOLIPIDS AND CERTAIN CLOTTING FACTORS IN PROTHROMBIN ACTIVATOR FORMATION. Biochim Biophys Acta. 1964; 90:436-9. DOI: 10.1016/0304-4165(64)90220-x. View

15.

Bangham A . A correlation between surface charge and coagulant action of phospholipids. Nature. 1961; 192:1197-8. DOI: 10.1038/1921197a0. View

16.

Barthels M, SEEGERS W . Substitution of lipids with bile salts in the formation of thrombin. Thromb Diath Haemorrh. 1969; 22(1):13-27. View

17.

SEEGERS W, Cole E, Aoki N . FUNCTION OF AC-GLOBULIN AND LIPID IN BLOOD CLOTTING. Can J Biochem Physiol. 1963; 41:2441-61. View

18.

Barton P, HANAHAN D . Some lipid-protein interactions involved in prothrombin activation. Biochim Biophys Acta. 1969; 187(3):319-27. DOI: 10.1016/0005-2760(69)90005-8. View

19.

STRITTMATTER P, Rogers M, Spatz L . The binding of cytochrome b 5 to liver microsomes. J Biol Chem. 1972; 247(22):7188-94. View

20.

Lux S, John K, Fleischer S, Jackson R, Gotto Jr A . Identification of the lipid-binding cyanogen bromide fragment from the cystine-containing high density apolipoprotein, APOLP-GLN-II. Biochem Biophys Res Commun. 1972; 49(1):23-9. DOI: 10.1016/0006-291x(72)90004-6. View