A Three-Dimensional Consideration of Variant Human Fibrinogens

Stephen J. Everse; Glen Spraggon; Russell F. Doolittle

doi:10.1055/s-0037-1615130

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1998; 80(01): 1-9
DOI: 10.1055/s-0037-1615130

Review Articles

Schattauer GmbH

A Three-Dimensional Consideration of Variant Human Fibrinogens

Stephen J. Everse

¹From the Center for Molecular Genetics, Univ. California, San Diego, La Jolla, CA, USA

,

Glen Spraggon

¹From the Center for Molecular Genetics, Univ. California, San Diego, La Jolla, CA, USA

,

Russell F. Doolittle

¹From the Center for Molecular Genetics, Univ. California, San Diego, La Jolla, CA, USA

› Author Affiliations

Abstract

Summary

Recently reported X-ray structures for large core fragments derived from human fibrinogen and fibrin make it possible to correlate structural and functional anomalies of known genetic variants. Here we examine a variety of amino acid replacements previously reported for hereditary dysfibrinogenemias, most of which are associated with impaired fibrin polymerization. For many of these we have modeled in the mutant amino acid and considered the structural consequences. We have also examined the cases of a small deletion and a large insertion, as well as the impact of substitutions in the GPRPam ligand that was co-crystallized with fragment double-D.

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References

References
1 Perutz MF, Lehmann H. Molecular pathology of human haemoglobin.. Nature 1968; 219: 902-9.
2 Yee VC, Pratt KP, Cote HC, LeTrong I, Chung DW, Davie EW, Stenkamp RE, Teller DC. Crystal structure of a 30 kDa C-terminal fragment from the γ chain of human fibrinogen.. Structure 1997; 5: 125-38.
3 Pratt KP, Cote HCF, Chung DW, Stenkamp RE, Davie EW. The fibrin polymerization pocket: three-dimensional structure of a 30-kDA C-terminal γ chain fragment complexed with the peptide Gly-Pro-Arg-Pro.. Proc Natl Acad Sci USA 1997; 94: 7176-81.
4 Spraggon G, Everse S, Doolittle RF. Crystal structures of fragment D from human fibrinogen and its crosslinked counterpart from fibrin.. Nature 1997; 389: 455-62.
5 Haverkate F, Samama M. Familial dysfibrinogenemia and thrombophilia.. Thromb Haemost 1995; 73: 151-61.
6 Menache D.. Congenital fibrinogen abnormalities.. Ann NY Acad Sci 1983; 408: 121-9.
7 Rupp C, Beck EA. Congenital dysfibrinogenemia.. Curr Prob Clin Biochem 1984; 14: 65-130.
8 Galanakis D. Inherited dysfibrinogenemia: emerging abnormal structure associations with pathologic and nonpathologic dysfunctions.. Semin Thromb Hemostasis 1993; 19: 386-95.
9 Matsuda M. The structure-function relationship of hereditary dysfibrinogens.. Intern J Hematol 1996; 64: 167-79.
10 Ebert RF. (ed) 1994 Index of variant human fibrinogens.. CRC Press; Boca Raton, Florida.:
11 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: 3085-9.
12 Laudano AP, Doolittle RF. Studies on synthetic peptides that bind to fibrinogen and prevent fibrin polymerization. Structural requirements, number of binding sites, and species differences.. Biochemistry 1980; 19: 1013-9.
13 Hantgan RR, Hermans J. Assembly of fibrin. A light scattering study.. J Biol Chem 1979; 254: 11272-81.
14 Jamney PA. Gel formation by fibrin oligomers without addition of monomers.. Biopolymers 1986; 25: 1337-44.
15 Chen R, Doolittle RF. γ-γ Cross-linking sites in human and Bovine fibrin.. Biochemistry 1971; 10: 4486-91.
16 McKee PA, Mattock O, Hill RL. Subunit structure of human fibrinogen, soluble fibrin, and crosslinked insoluble fibrin.. Proc Natl Acad Sci USA 1970; 66: 738-44.
17 Laurent TC, Blombäck B.. On the significance of the release of two different peptides from fibrinogen during clotting.. Acta Chem Scand 1958; 12: 1875-977.
18 Doolittle RF, Cassman KG, Chen R, Sharp JJ, Wooding GL. Correlation of the mode of fibrin formation with the pattern of cross-linking.. Ann NY Acad Sci 1972; 202: 114-26.
19 Doolittle RF. Structural aspects of the fibrinogen to fibrin conversion.. Adv Protein Chem 1973; 27: 1-109.
20 Blomback B, Hessel B, Hogg D, Thirkildsen L. A two-step fibrinogenfibrin transition in blood coagulation.. Nature 1978; 275: 501-5.
21 Palmer GR, Fritz OG. Quasielastic light-scattering studies on human fibrinogen and fibrin. II Fibrin polymerization.. Biopolymers 1979; 18: 1659-72.
22 Olexa SA, Budzynski A. Evidence for four different polymerization sites involved in human fibrin formation.. Proc Natl Acad Sci USA 1980; 77: 1374-8.
23 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: 9276-82.
24 Lewis SD, Shields PP, Shafer JA. Characterization of the kinetic pathway for liberation of fibrinopeptides during assembly of fibrin.. J Biol Chem 1985; 260: 10192-9.
25 Hasegawa N, Sasaki S. Location of the binding site “b” for lateral polymerization of fibrin.. Thromb Res 1990; 57: 183-95.
26 Weisel JW. Lateral aggregation and the role of the two pairs of fibrinopep-tides.. Biophys J 1986; 50: 1079-93.
27 Weisel JW, Nagaswami C. Computer modeling of fibrin polymerization kinetics correlated with electron microscope and turbidity obervations: clot structure and assembly are kinetically controlled.. Biophys J 1992; 63: 111-28.
28 Weisel JW, Veklich Y, Gorkun O. The sequence of cleavage of fibrinopep-tides from fibrinogen is important for protofibril formation and enhancement of lateral aggregation in fibrin clots.. J Mol Biol 1993; 232: 285-97.
29 Vindigni A, Di Cera E. Release of fibrinopeptides by the slow and fast forms of thrombin.. Biochemistry 1996; 35: 4417-26.
30 Kay D, Cuddigan BJ. The fine structure of fibrin.. Brit J Haemat 1967; 13: 341-7.
31 Medved LV, Litvinovich SV, Ugarova TP, Lukinova NI, Kalikhevich VN, Ardemasova ZA. Localization of a fibrin polymerization site complementary to Gly-His-Arg sequence.. FEBS Lett 1993; 320: 239-42.
32 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, In Press)
33 Gorkun OV, Veklich YI, Medved LV, Henschen AH, Weisel JW. Role of the αC domains of fibrin in clot formation.. Biochemistry. 1994; 33: 6986-97.
34 Medved LV, Gorkun OV, Manyakov VF, Belitser VA. The role of fibrinogen αC-domains in the fibrin assembly process.. FEBS Lett 1985; 181: 109-12.
35 Rosenberg JB, Newman PJ, Mosesson MW, Guillen M-C, Amrani DL. Paris I dysfibrinogenemia: a point mutation in intron 8 results in insertion of a 15 amino acid sequence in the fibrinogen γ chain.. Thromb Haemost 1993; 69: 217-20.
36 Yamazumi K, Shimura K, Terukina S, Takahashi N, Matsuda M. A γ-methionine-310 to threonine substitution and consequent N-glycosylation at γ-asparagine-308 identified in a congenital dysfibrinogenemia associated with posttraumatic bleeding, fibrinogen Asahi.. J Clin Invest 1989; 83: 1590-7.
37 Koopman J, Haverkate F, Grimbergen J, Egbring R, Lord ST. Fibrinogen Marburg: a homozygous case of dysfibrinogenemia, lacking amino acids Aa 461-610 (Lys 461 AAA > Stop TAA).. Blood 1992; 80: 1972-9.
38 Uemichi T, Liepnieks JJ, Yamada T, Gertz MA, Bang N, Benson MD. A frame shift mutation in the fibrinogen Aa chain gene in a kindred with renal amyloidosis.. Blood 1996; 87: 4197-203.
39 Uemichi TM Liepnieks JJ, Benson MD. Hereditary renal amyloidosis with a novel variant fibrinogen.. J Clin Invest 1994; 93: 731-6.
40 Benson MD, Liepnieks J, Uemichi T, Wheeler G, Correa R. Hereditary renal amyloidosis associated with a mutant fibrinogen a-chain.. Nature Genetics 1993; 3: 252-5.
41 Steel DM, Whitehead AS. The major acute phase reactants: C-reactive protein, serum amyloid P component and serum amyloid A protein.. Immunology Today 1994; 2: 81-8.
42 Okumura N, Furihata K, Terasawa F, Nakagoshi R, Ueno I, Katsuyama T. Fibrinogen Matsumoto I: a γ364 Asp>His (GAT. CAT) substitution asociated with defective fibrin polymerization.. Thromb Haemost 1996; 75: 887-91.
43 Bentolila S, Samama MM, Conard J, Horellou MH, French P. Association of dysfibrinogenemia and thrombosis. Apropos of a family (fibrinogen Melun) and review of the literature (in French).. Annalen Med Interne 1995; 146: 575-80.
44 Terukina S, Yamazumi K, Okamoto K, Yamashita H, Ito Y, Matsuda M. Fibrinogen Kyoto III: a congenital dysfibrinogen with a γ-aspartic acid-330 to tyrosine substitution.. Blood 1989; 74: 2681-7.
45 Reber P, Furlan M, Rupp C, Kehl M, Henschen A, Mannucci P, Beck E. Characterization of fibrinogen Milano I: amino acid exchange γ330 Asp→Val impairs fibrin polymerization.. Blood 1986; 67: 1751-6.
46 Miyata T, Furukawa K, Iwanaga S, Takamatsu J, Saito H. Fibrinogen Nagoya, a replacement of glutamine-329 by arginine in the γ-chain that impairs the polymerization of fibrin monomer.. J Biochem 1989; 105: 10-4.
47 Yoshida N, Hirata H, Morigami Y, Imaoka S, Matsuda M, Yamazumi K, Asakura S. Characterization of an abnormal fibrinogen Osaka V with the replacement of γ-arginine 375 by glycine.. J Biol Chem 1992; 267: 2753-9.
48 Wada Y, Niwa K, Maekawa H, Asakura S, Sugo T, Nakanishi M, Auerswald G, Popp M, Matsuda M. A new type of congenital dysfibrinogen, fibrinogen Bremen, with an Aα Gly-17 to Val substitution associated with hemorrhagic diathesis and delayed wound healing.. Thromb Haemost 1993; 70: 397-403.
49 Uotani C, Miyata T, Kumabashiri I, Asakura H, Saito M, Matsuda T, Kajiyama S, Iwanaga S. Fibrinogen Kanazawa: a congenital dysfibrinogenemia with delayed polymerization having a replacement of proline-18 by leucine in the Aa-chain.. Blood Coag Fibrinolysis 1991; 2: 413-7.
50 Yoshida N, Okuma M, Jirata H, Matsuda M, Yamazumi K, Asakura S. Fibrinogen Kyoto II, a new congenitally abnormal molecule, characterized by the replacement of Aα proline-18 by leucine.. Blood 1991; 78: 149-53.
51 Blomback M, Blomback B, Mammen EF, Prasad AS. Fibrinogen Detroit-A molecular defect in the N-terminal disulphide knot of human fibrinogen?. Nature 968 218: 134-7.
52 Hessel B, Stenbjerg S, Dyr J, Kudryk B, Therkildsen L, Blomback B. Fibrinogen Aarhus – a new case of dysfibrinogenemia.. Thromb Res 1986; 42: 21-37.
53 Dempfle CEH, Henschen A. Fibrinogen Mannheim I-identification of an Aa19Arg > Gly substitution in dysfibrinogenemia associated with bleeding tendency.. In: Fibrinogen 4. Current Basic and Clinical Aspects.. Matsuda M, Iwanaga S, Takada A, Henschen A. eds. Amsterdam: Elsevier Science Publ; 1990. pp. 159-66.
54 Henschen A, Kehl M, Southan C, Lottspeich F, Georgopoulos D. Genetically abnormal fibrinogens – some current characterization strategies.. In: Fibrinogen-Structure, Functional Aspects, Metabolism.. Haverkate F, Henschen A, Nieuwenhuizen W, Straub PW. eds. Berlin: Walter de Gruyter; 1983. pp. 125-44.
55 Matsuda M, Nakamikawa C, Baba M, Morimoto K. Fibrinogen Tokyo II: an abnormal fibrinogen with an impaired polymerization site on the aligned DD domain of fibrin molecules.. In: Fibrinogen-Structural Variants and Interactions.. Henschen A, Hessel B, McDonagh J, Saldeen T. eds. Berlin: Walter de Gruyter; 1985. pp. 213-22.
56 Matsuda M, Baba M, Morimoto K, Nakamikawa C. An abnormal fibrinogen with an impaired polymerization site on the aligned DD domain of fibrin molecules.. J Clin Invest 1983; 72: 1034-41.
57 Mosesson M, Siebenlist K, DiOrio J, Matsuda M, Hainfeld Wall J. The role of fibrinogen D domain intermolecular asociation sites in the polymerization of fibrin and fibrinogen Tokyo II (γ275 Arg→Cys).. J Clin Invest 1995; 96: 1053-8.
58 SYBYL Version 6.3, Oct. 1996. Tripos, Inc. St. Louis, MO.
59 Terukina S, Matsuda M, Hirata H, Takeda Y, Miyata T, Takao T, Shimonishi Y. Substitution of γArg-275 by Cys in an abnormal fibrinogen, “fibrinogen Osaka II”; evidence for a unique solitary cystine structure at the mutation site.. J Biol Chem 1986; 263: 13579-87.
60 Niwa K, Takebe M, Sugo T, Kawata Y, Mimuro J, Asakura S, Sakata Y, Mizushima J, Maeda A, Endo H, Matsuda M. A γ Gly-268 to Glu substitution is responsible for impaired fibrin assembly in a homozygous dysfibrinogen Kurashiki I.. Blood 1996; 87: 4686-94.
61 Bantia S, Bell WR, Dang CV. Polymerization defect of fibrinogen Baltimore III due to a gamma Asn-308 > Ile mutation.. Blood 1990; 75: 1659-63.
62 Yoshida N, Okuma M, Moroi M, Matsuda M. A lower molecular weight γ-chain variant in a congenital abnormal fibrinogen (Kyoto).. Blood 1986; 68: 703-7.
63 Grailhe P, Boyer-Neumann C, Haverkate F, Grimbergen J, Larrieu MJ, Angles-Cano E. The mutation in fibrinogen Bicetre II (γAsn308>Lys) does not affect the binding of t-PA and plasminogen to fibrin.. Blood Coag Fibrinolysis 1993; 4: 679-87.
64 Okumura N, Furihata K, Terasawa M, Ishikawa S, Ueno I, Katsuyama T. Fibrinogen Matsumoto II: γ308Asn>Lys (AAT>AAG) mutation associated with bleeding tendency.. Brit J Haematol 1996; 94: 526-8.
65 Yamazumi K, Shimura K, Maekawa H, Muramatsu S, Terukina S, Matsuda M. Delayed intermolecular γ-chain cross-linking by factor XIIIa in fibrinogen Asahi characterized by γ-Met-310 to Thr substitution with an N-glycosylated γ-Asn-308.. Blood Coag Fibrinolysis 1990; 1: 557-9.
66 Steinmann C, Reber P, Jungo M, Heinemann G, Wermuth B, Furlan M. Fibrinogen Bern I: substitution of γ337Asn > Lys is responsible for defective fibrin monomer polymerization.. Blood 1993; 82: 2104-8.
67 Furlan M, Stuckl B, Steinmann C, Jungo M, Lammle B. Normal binding of calcium to five fibrinogen variants with mutations in the carboxy terminal part of the γ-chain.. Thromb Haemost 1996; 76: 377-83.
68 Steinmann C, Bogli C, Iungo M, Lammle B, Heinemann G, Redaelli R, Baudo F, Furlan M. A new substitution γ-358 Ser > Cys, in fibrinogen Milano VII causes defective fibrinogen polymerization.. Thromb Haemost 1993; 62: 962 (abstract).
69 Maekawa H, Yamazumi K, Muramatsu S, Kaneko M, Hirata H, Takahashi N, Arocha-Piñango C, Rodriguez S, Nagy H, Perez-Requejo J, Matsuda M. Fibrinogen Lima: a homozygous dysfibrinogen with an Aa-arginine-141 to serine substitution associated with extra N-glycosylation at Aα-asparagine-139.. J Clin Invest 1992; 90: 67-76.
70 Kaudewitz H, Henschen A, Soria J, Soria C. Fibrinogen Pontoise: a genetically abnormal fibrinogen with defective polymerization but normal fibrinopeptide release.. In: Fibrinogen, Fibrin Formation and Fibrinolysis. eds. Lane DA, Henschen A, Jasani MK. Walter de Gruyter; Berlin: 1986. pp. 91-6.
71 Townsend RR, Hilliker E, Li YT, Laine RA, Bell WR, Lee YC. Carbohydrate structure of human fibrinogen.. J Biol Chem 1982; 257: 9704-10.
72 Beck B. Abnormal fibrinogen (fibrinogen “Baltimore”) as a cause of a familial hemrrhagic disorder.. Blood 1964; 24: 853-4.
73 Bantia S, Mane SM, Bell WR, Dang CV. Fibrinogen Baltimore I: polymerization defect associated with a γ292Gly > Val(GCC > GTC) mutation.. Blood 1990; 76: 2279-83.
74 Ramachandran GN, Sassiekharan V. Conformation of polypeptides and proteins.. Adv Prot Chem 1968; 28: 283-437.
75 Doolittle RF. A detailed consideration of a principal domain of vertebrate fibrinogen and its relatives.. Protein Sci 1992; 1: 1563-77.
76 Menache D. Constitutional and abnormal fibrinogen.. Thromb Diath Haemorrh 1964; (Suppl. 13) 173-85.
77 Budzynski AZ, Marder VJ, Menache D, Guillin MC. Defect in the gamma polypeptide chain of a congenital abnormal fibrinogen (Paris I).. Nature 1974; 252: 66-8.
78 Haverkate F, Timan G. Protective effect of calcium in the plasmin degradation of fibrinogen and fibrin fragments.. Thromb Res 1977; 10: 803-12.
79 Dang CV, Ebert RF, Bell WR. Localization of a fibrinogen calcium binding site between γ-subunit positions 311 and 336 by terbium fluorescence.. J Biol Chem 1985; 260: 9713-7.
80 Koopman J, Haverkate F, Briët E, Lord ST. A congenitally abnormal fibrinogen (Vlissingen) with a 6-base deletion in the γ chain causing defective calcium binding and impaired fibrin polymerization.. J Biol Chem 1991; 266: 13456-61.
81 Marx G. Protofibrin clots induced by calcium and zinc.. Biopolymers 1987; 26: 911-20.
82 Pan Y, Doolittle RF. cDNA sequence of a second fibrinogen α chain in lamprey: An archetypal version alignable with full-length β and γ chains.. Proc Natl Acad Sci USA 1992; 89: 2066-70.
83 Fu Y, Weissbach Plant PW, Oddoux C, Cao Y, Liang TJ, Roy SN, Redman CM, Grieninger G. Carboxy-terminal-extended variant of the human fibrinogen α subunit: a novel exon conferring marked homology to β and γ subunits.. Biochemistry 1992; 31: 11968-72.
84 Kraulis PJ. MOLSCRIPT: a program to produce both detailed and schematic plots of protein structures.. J Appl Crystallogr 1991; 24: 946-50.
85 Esnouf RM. An extensively modified version of Molscript which includes greatly enhanced colouring capabilities.. J Mol Graphics 1997; 15: 133-8.
86 Merritt EA, Murphy MEP. Raster 3D version 2.0: a program for photo-realistic molecular graphics.. Acta Crystallog 1994; D50: 869-73.