Ukr.Biochem.J. 2020; Volume 92, Issue 3, May-Jun, pp. 22-32

doi: https://doi.org/10.15407/ubj92.03.022

Structure and function of fibrinogen BβN-domains

04.08.2020   Uncategorized   No comments

L. Medved*, S. Yakovlev

Center for Vascular and Inflammatory Diseases and Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD, USA;
*e-mail: Lmedved@som.umaryland.edu

Received: 17 May 2020; Accepted: 30 June 2020

Fibrinogen is a polyfunctional plasma protein involved in various physiological and pathological processes through the interaction of its multiple domains with different ligands and cell receptors. Among fibrinogen domains, two BβN-domains are formed by the N-terminal portions of its two Bβ chains including­ amino acid residues Bβ1-64. Although their folding status is not well understood and the recombinant disulfide-linked (Bβ1-66)2  fragment corresponding to a pair of these domains was found to be unfolded, some data suggest that these domains may be folded in the parent molecule. In contrast, their major functional properties are well established. Removal of fibrinopeptides B (amino acid residues Bβ1-14) from these domains upon fibrinogen to fibrin conversion results in the exposure of multiple binding sites in fibrin βN-domains (residues β15-64). These sites provide interaction of the βN-domains with different proteins and cells and their participation in various processes including fibrin assembly, fibrin-dependent angiogenesis, and fibrin-dependent leukocyte transmigration and thereby inflammation. The objective of this review is to summarize the current view of the structure and function of these domains in fibrinogen and fibrin and their role in the above-mentioned processes.

Keywords: , , , ,

References:

  1. Henschen A, McDonagh J. Fibrinogen, fibrin and factor XIII. In: Zwaal RFA, Hemker HC (Eds.) Blood Coagulation. Elsevier Science Publishers, Amsterdam, 1986. P. 171-241. CrossRef
  2. Medved L, Weisel JW, Fibrinogen and Factor XIII Subcommittee of Scientific Standardization Committee of International Society on Thrombosis and Haemostasis. Recommendations for nomenclature on fibrinogen and fibrin. J Thromb Haemost. 2009;7(2):355-9. PubMed, PubMedCentral, CrossRef
  3. Privalov PL, Medved LV. Domains in the fibrinogen molecule. J Mol Biol. 1982;159(4):665-83. PubMed, CrossRef
  4. Medved LV, Gorkun OV, Privalov PL. Structural organization of C-terminal parts of fibrinogen A alpha-chains. FEBS Lett. 1983;160(1-2):291-5. PubMed, CrossRef
  5. Medved’ LV, Litvinovich SV, Privalov PL. Domain organization of the terminal parts in the fibrinogen molecule. FEBS Lett. 1986;202(2):298-302. PubMed, CrossRef
  6. Medved L, Litvinovich S, Ugarova T, Matsukav Y, Ingham K. Domain structure and functional activity of the recombinant human fibrinogen gamma-module (gamma148-411). Biochemistry. 1997;36(15):4685-93. PubMed, CrossRef
  7. Pratt KP, Côté HC, Chung DW, Stenkamp RE, Davie EW. The primary fibrin polymerization pocket: three-dimensional structure of a 30-kDa C-terminal gamma chain fragment complexed with the peptide Gly-Pro-Arg-Pro. Proc Natl Acad Sci USA. 1997;94(14):7176-81. PubMed, PubMedCentral, CrossRef
  8. Spraggon G, Everse SJ, Doolittle RF. Crystal structures of fragment D from human fibrinogen and its crosslinked counterpart from fibrin. Nature. 1997;389(6650):455-62. PubMed, CrossRef
  9. Brown JH, Volkmann N, Jun G, Henschen-Edman AH, Cohen C. The crystal structure of modified bovine fibrinogen. Proc Natl Acad Sci USA. 2000;97(1):85-90. PubMed, PubMedCentral, CrossRef
  10. Yang Z, Mochalkin I, Veerapandian L, Riley M, Doolittle RF. Crystal structure of native chicken fibrinogen at 5.5-A resolution. Proc Natl Acad Sci USA. 2000;97(8):3907-12. PubMed, PubMedCentral, CrossRef
  11. Yang Z, Kollman JM, Pandi L, Doolittle RF. Crystal structure of native chicken fibrinogen at 2.7 A resolution. Biochemistry. 2001;40(42):12515-23. PubMed, CrossRef
  12. Madrazo J, Brown JH, Litvinovich S, Dominguez R, Yakovlev S, Medved L, Cohen C. Crystal structure of the central region of bovine fibrinogen (E5 fragment) at 1.4-A resolution. Proc Natl Acad Sci USA. 2001;98(21):11967-72. PubMed, PubMedCentral, CrossRef
  13. Pechik I,Madrazo J, Mosesson MW, Hernandez I, Gilliland GL, Medved L. Crystal structure of the complex between thrombin and the central “E” region of fibrin. Proc Natl Acad Sci USA. 2004;101(9):2718-23. PubMed, PubMedCentral, CrossRef
  14. Kollman JM, Pandi L, Sawaya MR, Riley M, Doolittle RF. Crystal structure of human fibrinogen. Biochemistry. 2009;48(18):3877-86. PubMed, CrossRef
  15. Burton RA, Tsurupa G, Medved L, Tjandra N. Identification of an ordered compact structure within the recombinant bovine fibrinogen alphaC-domain fragment by NMR. Biochemistry. 2006;45(7):2257-66. PubMed, PubMedCentral, CrossRef
  16. Burton RA, Tsurupa G, Hantgan RR, Tjandra N, Medved L. NMR solution structure, stability, and interaction of the recombinant bovine fibrinogen alphaC-domain fragment. Biochemistry. 2007;46(29):8550-60. PubMed, PubMedCentral, CrossRef
  17. Tsurupa G, Hantgan RR, Burton RA, Pechik I, Tjandra N, Medved L. Structure, stability, and interaction of the fibrin(ogen) alphaC-domains. Biochemistry. 2009;48(51):12191-201. PubMed, PubMedCentral, CrossRef
  18. Gorlatov S, Medved L. Interaction of fibrin(ogen) with the endothelial cell receptor VE-cadherin: mapping of the receptor-binding site in the NH2-terminal portions of the fibrin beta chains. Biochemistry. 2002;41(12):4107-16. PubMed, CrossRef
  19. Pandya BV, Gabriel JL, O’Brien J, Budzynski AZ. Polymerization site in the beta chain of fibrin: mapping of the B beta 1-55 sequence. Biochemistry. 1991;30(1):162-8. PubMed, CrossRef
  20. Chernyshenko VO, Volynets GP. Predicting of fibrinogen ВβN-domain conformation by computer modeling and limited proteolysis. Ukr Bioorg Acta. 2011;9(1): 53-57.
  21. Litvinov RI, Yakovlev S, Tsurupa G, Gorkun OV, Medved L, Weisel JW. Direct evidence for specific interactions of the fibrinogen alphaC-domains with the central E region and with each other. Biochemistry. 2007;46(31):9133-42.  PubMed, PubMedCentral, CrossRef
  22. Blomback B, Blomback M, Nilsson IM. Coagulation studies on “Reptilase”, an extract of the venom from Bothrops jararaca. Thromb Diath Haemorrh. 1958;1(1):76-86. PubMed, CrossRef
  23. Weisel JW, Litvinov RI. Mechanisms of fibrin polymerization and clinical implications. Blood. 2013;121(10):1712-9. PubMed, PubMedCentral, CrossRef
  24. Collet JP, Park D, Lesty C, Soria J, Soria C, Montalescot G, Weisel JW. Influence of fibrin network conformation and fibrin fiber diameter on fibrinolysis speed: dynamic and structural approaches by confocal microscopy. Arterioscler Thromb Vasc Biol. 2000;20(5):1354-61. PubMed, CrossRef
  25. Collet JP, Lesty C, Montalescot G, Weisel JW. Dynamic changes of fibrin architecture during fibrin formation and intrinsic fibrinolysis of fibrin-rich clots. J Biol Chem. 2003; 278(24): 21331-21335. PubMed, CrossRef
  26. Weisel JW, Veklich Y, Gorkun O. The sequence of cleavage of fibrinopeptides from fibrinogen is important for protofibril formation and enhancement of lateral aggregation in fibrin clots. J Mol Biol. 1993;232(1):285-97. PubMed, CrossRef
  27. Yang Z, Mochalkin I, Doolittle RF. A model of fibrin formation based on crystal structures of fibrinogen and fibrin fragments complexed with synthetic peptides. Proc Natl Acad Sci USA. 2000;97(26):14156-61. PubMed, PubMedCentral, CrossRef
  28. Everse SJ, Spraggon G, Veerapandian L, Riley M, Doolittle RF. Crystal structure of fragment double-D from human fibrin with two different bound ligands. Biochemistry. 1998; 37(24): 8637-8642. PubMed, CrossRef
  29. Laudano AP, Doolittle RF. Synthetic peptide derivatives that bind to fibrinogen and prevent the polymerization of fibrin monomers. Proc Natl Acad Sci USA. 1978; 75(7): 3085-3089. PubMed, PubMedCentral, CrossRef
  30. Laudano AP, Cottrell BA, Doolittle RF. Synthetic peptides modeled on fibrin polymerization sites. Ann N Y Acad Sci. 1983; 408: 315-329. PubMed, CrossRef
  31. Blombäck B, Hessel B, Hogg D, Therkildsen L. A two-step fibrinogen-fibrin transition in blood coagulation. Nature. 1978; 275(5680): 501-505. PubMed, CrossRef
  32. Weisel JW. Fibrinogen and fibrin. Adv Protein Chem. 2005; 70: 247-299. PubMed, CrossRef
  33. Martinelli RA, Scheraga HA.  Steady-state kinetic study of the bovine thrombin-fibrinogen interaction. Biochemistry. 1980;19(11):2343-50. PubMed, CrossRef
  34. Hurlet-Jensen A, Cummins HZ, Nossel HL, Liu CY. Fibrin polymerization and release of fibrinopeptide B by thrombin. Thromb Res. 1982;27(4):419-27. PubMed, CrossRef
  35. Higgins DL, Lewis SD, Shafer JA. Steady state kinetic parameters for the thrombin-catalyzed conversion of human fibrinogen to fibrin.  J Biol Chem. 1983;258(15):9276-82. PubMed
  36. Pechik I, Yakovlev S, Mosesson MW, Gilliland GL, Medved L. Structural basis for sequential cleavage of fibrinopeptides upon fibrin assembly. Biochemistry. 2006;45(11):3588-97. PubMed, PubMedCentral, CrossRef
  37. Iozzo RV. Matrix proteoglycans: from molecular design to cellular function. Annu Rev Biochem. 1998;67:609-52. PubMed, CrossRef
  38. Bernfield M, Götte M, Park PW, Reizes O, Fitzgerald ML, Lincecum J, Zako M. Functions of cell surface heparan sulfate proteoglycans. Annu Rev Biochem. 1999;68:729-77.  PubMed, CrossRef
  39. Sasisekharan R, Venkataraman G. Heparin and heparan sulfate: biosynthesis, structure and function. Curr Opin Chem Biol. 2000;4(6):626-31. PubMed, CrossRef
  40. Esko JD, Lindahl U. Molecular diversity of heparan sulfate. J Clin Invest. 2001;108(2):169-73. PubMed, PubMedCentral, CrossRef
  41. Scully MF, Ellis V, Kakkar VV. Localisation of heparin in mast cells. Lancet. 1986;2(8509):718-9. PubMed, CrossRef
  42. Capila I, Linhardt RJ. Heparin-protein interactions. Angew Chem Int Ed Engl. 2002;41(3):391-412. PubMed
  43. Whinna HC, Church FC. Interaction of thrombin with antithrombin, heparin cofactor II, and protein C inhibitor. J Protein Chem. 1993;12(6):677-88. PubMed, CrossRef
  44. Li W, Johnson DJ, Esmon CT, Huntington JA. Structure of the antithrombin-thrombin-heparin ternary complex reveals the antithrombotic mechanism of heparin. Nat Struct Mol Biol. 2004;11(9):857-62. PubMed, CrossRef
  45. Hogg PJ, Jackson CM. Formation of a ternary complex between thrombin, fibrin monomer, and heparin influences the action of thrombin on its substrates. J Biol Chem. 1990;265(1):248-55. PubMed
  46. Hogg PJ, Jackson CM. Fibrin monomer protects thrombin from inactivation by heparin-antithrombin III: implications for heparin efficacy. Proc Natl Acad Sci USA. 1989;86(10):3619-23. PubMed, PubMedCentral, CrossRef
  47. Hogg PJ, Jackson CM. Heparin promotes the binding of thrombin to fibrin polymer. Quantitative characterization of a thrombin-fibrin polymer-heparin ternary complex. J Biol Chem. 1990;265(1):241-7. PubMed
  48. Hogg PJ, Bock PE. Modulation of thrombin and heparin activities by fibrin. Thromb Haemost. 1997;77(3):424-33. PubMed
  49. Odrljin TM, Francis CW, Sporn LA, Bunce LA, Marder VJ, Simpson-Haidaris PJ. Heparin-binding domain of fibrin mediates its binding to endothelial cells. Arterioscler Thromb Vasc Biol. 1996;16(12):1544-51. PubMed, CrossRef
  50. Retzinger GS, Chandler LJ, Cook BC. Complexation with heparin prevents adhesion between fibrin-coated surfaces. J Biol Chem. 1992;267(34):24356-62. PubMed
  51. Mohri H, Ohkubo T. Fibrinogen binds to heparin: the relationship of the binding of other adhesive proteins to heparin. Arch Biochem Biophys. 1993;303(1):27-31. PubMed, CrossRef
  52. Raut S, Gaffney PJ. Interaction of heparin with fibrinogen using surface plasmon resonance technology: investigation of heparin binding site on fibrinogen. Thromb Res. 1996;81(4):503-9. PubMed, CrossRef
  53. Odrljin TM, Shainoff JR, Lawrence SO, Simpson-Haidaris PJ. Thrombin cleavage enhances exposure of a heparin binding domain in the N-terminus of the fibrin beta chain. Blood. 1996;88(6):2050-61. PubMed, CrossRef
  54. Mohri H, Iwamatsu A, Ohkubo T. Heparin binding sites are located in a 40-kD γ-chain and a 36-kD β-chain fragment isolated from human fibrinogen. J Thromb Thrombolysis. 1994; 1(1): 49-54. PubMed, CrossRef
  55. Skogen WF, Wilner GD. A simple one-step HPLC procedure for the purification of the NH2-terminal plasmin-derived B beta 1-42 peptide of human fibrinogen. Thromb Res. 1986;41(2):161-6. PubMed, CrossRef
  56. Pandya BV, Rubin RN, Olexa SA, Budzynski AZ. Unique degradation of human fibrinogen by proteases from western diamondback rattlesnake (Crotalus atrox) venom. Toxicon. 1983; 21(4): 515-526. PubMed, CrossRef
  57. Pandya BV, Budzynski AZ. Anticoagulant proteases from western diamondback rattlesnake (Crotalus atrox) venom. Biochemistry. 1984;23(3):460-70. PubMed, CrossRef
  58. Pandya BV, Cierniewski CS, Budzynski AZ. Conservation of human fibrinogen conformation after cleavage of the B beta chain NH2 terminus. J Biol Chem. 1985;260(5):2994-3000. PubMed
  59. Yakovlev S, Gorlatov S, Ingham K, Medved L. Interaction of fibrin(ogen) with heparin: further characterization and localization of the heparin-binding site. Biochemistry. 2003;42(25):7709-16. PubMed, CrossRef
  60. Brasch J, Harrison OJ, Honig B, Shapiro L. Thinking outside the cell: how cadherins drive adhesion. Trends Cell Biol. 2012;22(6):299-310. PubMed, PubMedCentral, CrossRef
  61. Martinez J, Ferber A, Bach TL, Yaen CH. Interaction of fibrin with VE-cadherin. Ann N Y Acad Sci. 2001;936:386-405. PubMed, CrossRef
  62. Folkman J. Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med. 1995;1(1):27-31. PubMed, CrossRef
  63. Ware JA, Simons M. Angiogenesis in ischemic heart disease. Nat Med. 1997;3(2):158-64. PubMed, CrossRef
  64. Tonnesen MG, Feng X, Clark RA. Angiogenesis in wound healing. J Investig Dermatol Symp Proc. 2000;5(1):40-6. PubMed, CrossRef
  65. Conway EM, Collen D, Carmeliet P. Molecular mechanisms of blood vessel growth. Cardiovasc Res. 2001;49(3):507-21. PubMed, CrossRef
  66. Montesano R, Pepper MS, Vassalli JD, Orci L. Phorbol ester induces cultured endothelial cells to invade a fibrin matrix in the presence of fibrinolytic inhibitors. J Cell Physiol. 1987;132(3):509-16. PubMed, CrossRef
  67. Nicosia RF, Ottinetti A. Modulation of microvascular growth and morphogenesis by reconstituted basement membrane gel in three-dimensional cultures of rat aorta: a comparative study of angiogenesis in matrigel, collagen, fibrin, and plasma clot. In Vitro Cell Dev Biol. 1990;26(2):119-28. PubMed, CrossRef
  68. Chalupowicz DG, Chowdhury ZA, Bach TL, Barsigian C, Martinez J. Fibrin II induces endothelial cell capillary tube formation. J Cell Biol. 1995;130(1):207-15. PubMed, PubMedCentral, CrossRef
  69. Bach TL, Barsigian C, Chalupowicz DG, Busler D, Yaen CH, Grant DS, Martinez J. VE-Cadherin mediates endothelial cell capillary tube formation in fibrin and collagen gels. Exp Cell Res. 1998;238(2):324-34. PubMed, CrossRef
  70. Bach TL, Barsigian C, Yaen CH, Martinez J. Endothelial cell VE-cadherin functions as a receptor for the beta15-42 sequence of fibrin. J Biol Chem. 1998;273(46):30719-28. PubMed, CrossRef
  71. Procyk R, Kudryk B, Callender S, Blombäck B. Accessibility of epitopes on fibrin clots and fibrinogen gels. Blood. 1991;77(7):1469-75. PubMed, CrossRef
  72. Harris ES, Nelson WJ. VE-cadherin: at the front, center, and sides of endothelial cell organization and function. Curr Opin Cell Biol. 2010;22(5):651-8. PubMed, PubMedCentral, CrossRef
  73. Dejana E, Tournier-Lasserve E, Weinstein BM. The control of vascular integrity by endothelial cell junctions: molecular basis and pathological implications. Dev Cell. 2009;16(2):209-21. PubMed, CrossRef
  74. Yakovlev S, Medved L. Interaction of fibrin(ogen) with the endothelial cell receptor VE-cadherin: localization of the fibrin-binding site within the third extracellular VE-cadherin domain. Biochemistry. 2009;48(23):5171-9. pm id=”19413351″], PubMedCentral, CrossRef
  75. Petzelbauer P, Zacharowski PA, Miyazaki Y, Friedl P, Wickenhauser G, Castellino FJ, Gröger M, Wolff K, Zacharowski K. The fibrin-derived peptide Bbeta15-42 protects the myocardium against ischemia-reperfusion injury. Nat Med. 2005;11(3):298-304. PubMed, CrossRef
  76. Zacharowski K, Zacharowski P, Reingruber S, Petzelbauer P. Fibrin(ogen) and its fragments in the pathophysiology and treatment of myocardial infarction. J Mol Med (Berl). 2006;84(6):469-77. PubMed, CrossRef
  77. Yakovlev S, Gao Y, Cao C, Chen L, Strickland DK, Zhang L, Medved L. Interaction of fibrin with VE-cadherin and anti-inflammatory effect of fibrin-derived fragments. J Thromb Haemost. 2011;9(9):1847-55. PubMed, PubMedCentral, CrossRef
  78. Yakovlev S, Cao C, Galisteo R, Zhang L, Strickland DK, Medved L. Fibrin-VLDL Receptor-Dependent Pathway Promotes Leukocyte Transmigration by Inhibiting Src Kinase Fyn and is a Target for Fibrin β15-42 Peptide. Thromb Haemost. 2019;119(11):1816-1826. PubMed, PubMedCentral, CrossRef
  79. Yakovlev S, Mikhailenko I, Cao C, Zhang L, Strickland DK, Medved L. Identification of VLDLR as a novel endothelial cell receptor for fibrin that modulates fibrin-dependent transendothelial migration of leukocytes. Blood. 2012;119(2):637-44. PubMed, PubMedCentral, CrossRef
  80. Yakovlev S, Medved L. Effect of fibrinogen, fibrin, and fibrin degradation products on transendothelial migration of leukocytes. Thromb Res. 2018;162:93-100. PubMed, PubMedCentral, CrossRef
  81. Yakovlev S, Medved L. Interaction of fibrin with the very low-density lipoprotein (VLDL) receptor: further characterization and localization of the VLDL receptor-binding site in fibrin βN-domains. Biochemistry. 2017; 56(19): 2518-2528. PubMed, PubMedCentral, CrossRef
  82. Yakovlev S, Medved L. Interaction of fibrin with the very low density lipoprotein receptor: further characterization and localization of the fibrin-binding site. Biochemistry. 2015; 54(30): 4751-4761. PubMed, PubMedCentral, CrossRef
  83. Banerjee K, Yakovlev S, Gruschus JM, Medved L, Tjandra N. Nuclear magnetic resonance solution structure of the recombinant fragment containing three fibrin-binding cysteine-rich domains of the very low density lipoprotein receptor. Biochemistry. 2018; 57(30): 4395-4403. PubMed, PubMedCentral, CrossRef
  84. Holinstat M, Knezevic N, Broman M, Samarel AM, Malik AB, Mehta D. Suppression of RhoA activity by focal adhesion kinase-induced activation of p190RhoGAP: role in regulation of endothelial permeability. J Biol Chem. 2006; 281(4): 2296-2305. PubMed, CrossRef
  85. Gröger M, Pasteiner W, Ignatyev G, Matt U, Knapp S, Atrasheuskaya A, Bukin E, Friedl P, Zinkl D, Hofer-Warbinek R, Zacharowski K, Petzelbauer P, Reingruber S. Peptide Bβ15-42 preserves endothelial barrier function in shock. PLoS One. 2009; 4(4): e5391. PubMed, PubMedCentral, CrossRef
  86. Yakovlev S, Belkin AM, Chen L, Cao C, Zhang L, Strickland DK, Medved L. Anti-VLDL receptor monoclonal antibodies inhibit fibrin-VLDL receptor interaction and reduce fibrin-dependent leukocyte transmigration. Thromb Haemost. 2016; 116(6): 1122-1130. PubMed, PubMedCentral, CrossRef
  87. Ruiz J, Kouiavskaia D, Migliorini M, Robinson S, Saenko EL, Gorlatova N, Li D, Lawrence D, Hyman BT, Weisgraber KH, Strickland DK. The apoE isoform binding properties of the VLDL receptor reveal marked differences from LRP and the LDL receptor. J Lipid Res. 2005; 46(8): 1721-1731. PubMed, CrossRef
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