Identification of distinct sequences in human blood coagulation factor Xa and prothrombin essential for substrate and cofactor recognition in the prothrombinase complex - PubMed

Affiliations

• PMID: 12805370
• DOI: 10.1074/jbc.M305906200

Free article

Identification of distinct sequences in human blood coagulation factor Xa and prothrombin essential for substrate and cofactor recognition in the prothrombinase complex

Subramanian Yegneswaran et al. J Biol Chem. 2003.

Free article

Abstract

To identify amino acid sequences in factor Xa (fXa) and prothrombin (fII) that may be involved in prothrombinase complex (fXa.factor Va.fII.phospholipids) assembly, synthetic peptides based on fXa and fII sequences were prepared and screened for their ability to inhibit fXa-induced clotting of normal plasma. One fII peptide (PT557-571 homologous to chymotrypsin (CHT) residues 225-239) and two fXa peptides (X404-418, CHT231-244, and X415-429, CHT241-252C) potently inhibited plasma clotting and prothrombinase activity with 50% inhibition between 41 and 115 microM peptide. Inhibition of prothrombinase by PT557-571 and X415-429 was fVa-independent, whereas the inhibition by X404-418 was fVa-dependent. X404-418 inhibited the binding of fVa to fluorescein-labeled, inhibited fXai in the presence of phosphatidylcholine/phosphatidylserine vesicles, whereas X415-429 inhibited binding of fII to phospholipid-bound fluorescein-labeled, inhibited fXai. PT557-571 altered the fluorescence emission of fluorescein-labeled fXai, showing that PT557-571 binds to fXai. These data suggest that residues 404-418 in fXa provide fVa binding sites, whereas residues 557-571 in fII and 415-429 in fXa mediate interactions between fXa and fII in the prothrombinase complex.

Similar articles

• Prothrombin residues 473-487 contribute to factor Va binding in the prothrombinase complex.

  Yegneswaran S, Mesters RM, Fernández JA, Griffin JH. Yegneswaran S, et al. J Biol Chem. 2004 Nov 19;279(47):49019-25. doi: 10.1074/jbc.M406645200. Epub 2004 Aug 25. J Biol Chem. 2004. PMID: 15331602

• Binding sites for blood coagulation factor Xa and protein S involving residues 493-506 in factor Va.

  Heeb MJ, Kojima Y, Hackeng TM, Griffin JH. Heeb MJ, et al. Protein Sci. 1996 Sep;5(9):1883-9. doi: 10.1002/pro.5560050914. Protein Sci. 1996. PMID: 8880912 Free PMC article.

• Membrane-dependent interaction of factor Xa and prothrombin with factor Va in the prothrombinase complex.

  Qureshi SH, Yang L, Manithody C, Rezaie AR. Qureshi SH, et al. Biochemistry. 2009 Jun 9;48(22):5034-41. doi: 10.1021/bi900240g. Biochemistry. 2009. PMID: 19378973 Free PMC article.

• Factor Va-factor Xa interactions: molecular sites involved in enzyme:cofactor assembly.

  Steen M. Steen M. Scand J Clin Lab Invest Suppl. 2002;237:5-11. doi: 10.1080/003655102762377439. Scand J Clin Lab Invest Suppl. 2002. PMID: 12570161 Review.

• Blood coagulation factor Va's key interactive residues and regions for prothrombinase assembly and prothrombin binding.

  Schreuder M, Reitsma PH, Bos MHA. Schreuder M, et al. J Thromb Haemost. 2019 Aug;17(8):1229-1239. doi: 10.1111/jth.14487. Epub 2019 Jun 17. J Thromb Haemost. 2019. PMID: 31102425 Free PMC article. Review.

Cited by

• Characterization of a human coagulation factor Xa-binding site on Viperidae snake venom phospholipases A2 by affinity binding studies and molecular bioinformatics.

  Faure G, Gowda VT, Maroun RC. Faure G, et al. BMC Struct Biol. 2007 Dec 6;7:82. doi: 10.1186/1472-6807-7-82. BMC Struct Biol. 2007. PMID: 18062812 Free PMC article.

• Probing prothrombin structure by limited proteolysis.

  Acquasaliente L, Pelc LA, Di Cera E. Acquasaliente L, et al. Sci Rep. 2019 Apr 16;9(1):6125. doi: 10.1038/s41598-019-42524-z. Sci Rep. 2019. PMID: 30992526 Free PMC article.

• Detecting phenotype-specific interactions between biological processes from microarray data and annotations.

  Ansari NA, Bao R, Voichiţa C, Drăghici S. Ansari NA, et al. IEEE/ACM Trans Comput Biol Bioinform. 2012 Sep-Oct;9(5):1399-409. doi: 10.1109/TCBB.2012.65. IEEE/ACM Trans Comput Biol Bioinform. 2012. PMID: 22547431 Free PMC article.

• Cryo-EM structure of the prothrombin-prothrombinase complex.

  Ruben EA, Summers B, Rau MJ, Fitzpatrick JAJ, Di Cera E. Ruben EA, et al. Blood. 2022 Jun 16;139(24):3463-3473. doi: 10.1182/blood.2022015807. Blood. 2022. PMID: 35427420 Free PMC article.

• Cryo-EM structures of coagulation factors.

  Di Cera E, Mohammed BM, Pelc LA, Stojanovski BM. Di Cera E, et al. Res Pract Thromb Haemost. 2022 Nov 2;6(7):e12830. doi: 10.1002/rth2.12830. eCollection 2022 Oct. Res Pract Thromb Haemost. 2022. PMID: 36349261 Free PMC article. Review.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Elsevier Science

• Other Literature Sources

  • The Lens - Patent Citations Database