Skip to main content
PMC home page
Protein Science : A Publication of the Protein Society logoLink to Protein Science : A Publication of the Protein Society
. 1992 Dec;1(12):1563–1577. doi: 10.1002/pro.5560011204

A detailed consideration of a principal domain of vertebrate fibrinogen and its relatives.

R F Doolittle 1
PMCID: PMC2142140  PMID: 1304888

Abstract

Vertebrate fibrinogen is a complex multidomained protein, the structure of which has been inferred mainly from electron microscopy and amino acid sequence studies. Among its most prominent features are two terminal globules, moieties that are mostly composed of the carboxyl-terminal two-thirds of the beta and gamma chains. Sequences homologous to the latter segments are found in several other animal proteins, always as the carboxyl-terminal contributions. An alignment of 15 amino acid sequences from various fibrinogens and related proteins has been used to make judgments about secondary structure. The nature of amino acids at each position in the alignment was used to distinguish alpha helices and beta structure on the one hand from loops and turns on the other, and the resulting assignments compared with predictions of secondary structure by other methods. Additionally, constraints imposed by the locations of cystines, carbohydrate attachment residues, and proteinase-sensitive points provided further insights into the general organization of the postulated secondary structures. Other ancillary data, including the effects of bound calcium and the locations of labeled or variant residues, were also considered. An intriguing similarity to a portion of the recently reported structure of a calcium-dependent lectin is noted.

Full Text

The Full Text of this article is available as a PDF (1.3 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Baker N. E., Mlodzik M., Rubin G. M. Spacing differentiation in the developing Drosophila eye: a fibrinogen-related lateral inhibitor encoded by scabrous. Science. 1990 Dec 7;250(4986):1370–1377. doi: 10.1126/science.2175046. [DOI] [PubMed] [Google Scholar]
  2. Benner S. A., Gerloff D. Patterns of divergence in homologous proteins as indicators of secondary and tertiary structure: a prediction of the structure of the catalytic domain of protein kinases. Adv Enzyme Regul. 1991;31:121–181. doi: 10.1016/0065-2571(91)90012-b. [DOI] [PubMed] [Google Scholar]
  3. Bohonus V. L., Doolittle R. F., Pontes M., Strong D. D. Complementary DNA sequence of lamprey fibrinogen beta chain. Biochemistry. 1986 Oct 21;25(21):6512–6516. doi: 10.1021/bi00369a026. [DOI] [PubMed] [Google Scholar]
  4. Bouma H., Takagi T., Doolittle R. F. The arrangement of disulfide bonds in fragment D from human fibrinogen. Thromb Res. 1978 Sep;13(3):557–562. doi: 10.1016/0049-3848(78)90142-1. [DOI] [PubMed] [Google Scholar]
  5. Bowie J. U., Lüthy R., Eisenberg D. A method to identify protein sequences that fold into a known three-dimensional structure. Science. 1991 Jul 12;253(5016):164–170. doi: 10.1126/science.1853201. [DOI] [PubMed] [Google Scholar]
  6. Budzynski A. Z. Difference in conformation of fibrinogen degradation products as revealed by hydrogen exchange and spectropolarimetry. Biochim Biophys Acta. 1971 Mar 23;229(3):663–671. doi: 10.1016/0005-2795(71)90282-0. [DOI] [PubMed] [Google Scholar]
  7. Chen R., Doolittle R. F. Isolation, characterization, and location of a donor-acceptor unit from cross-linked fibrin. Proc Natl Acad Sci U S A. 1970 Jun;66(2):472–479. doi: 10.1073/pnas.66.2.472. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Chou P. Y., Fasman G. D. Prediction of protein conformation. Biochemistry. 1974 Jan 15;13(2):222–245. doi: 10.1021/bi00699a002. [DOI] [PubMed] [Google Scholar]
  9. Crawford I. P., Niermann T., Kirschner K. Prediction of secondary structure by evolutionary comparison: application to the alpha subunit of tryptophan synthase. Proteins. 1987;2(2):118–129. doi: 10.1002/prot.340020206. [DOI] [PubMed] [Google Scholar]
  10. Dang C. V., Ebert R. F., Bell W. R. Localization of a fibrinogen calcium binding site between gamma-subunit positions 311 and 336 by terbium fluorescence. J Biol Chem. 1985 Aug 15;260(17):9713–9719. [PubMed] [Google Scholar]
  11. Doolittle R. F. Fibrinogen and fibrin. Annu Rev Biochem. 1984;53:195–229. doi: 10.1146/annurev.bi.53.070184.001211. [DOI] [PubMed] [Google Scholar]
  12. Doolittle R. F. Structural aspects of the fibrinogen to fibrin conversion. Adv Protein Chem. 1973;27:1–109. doi: 10.1016/s0065-3233(08)60446-5. [DOI] [PubMed] [Google Scholar]
  13. Drickamer K. Two distinct classes of carbohydrate-recognition domains in animal lectins. J Biol Chem. 1988 Jul 15;263(20):9557–9560. [PubMed] [Google Scholar]
  14. Feng D. F., Doolittle R. F. Progressive alignment and phylogenetic tree construction of protein sequences. Methods Enzymol. 1990;183:375–387. doi: 10.1016/0076-6879(90)83025-5. [DOI] [PubMed] [Google Scholar]
  15. Flaherty K. M., McKay D. B., Kabsch W., Holmes K. C. Similarity of the three-dimensional structures of actin and the ATPase fragment of a 70-kDa heat shock cognate protein. Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):5041–5045. doi: 10.1073/pnas.88.11.5041. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Fowler W. E., Erickson H. P. Trinodular structure of fibrinogen. Confirmation by both shadowing and negative stain electron microscopy. J Mol Biol. 1979 Oct 25;134(2):241–249. doi: 10.1016/0022-2836(79)90034-2. [DOI] [PubMed] [Google Scholar]
  17. Garnier J., Osguthorpe D. J., Robson B. Analysis of the accuracy and implications of simple methods for predicting the secondary structure of globular proteins. J Mol Biol. 1978 Mar 25;120(1):97–120. doi: 10.1016/0022-2836(78)90297-8. [DOI] [PubMed] [Google Scholar]
  18. Haverkate F., Timan G. Protective effect of calcium in the plasmin degradation of fibrinogen and fibrin fragments D. Thromb Res. 1977 Jun;10(6):803–812. doi: 10.1016/0049-3848(77)90137-2. [DOI] [PubMed] [Google Scholar]
  19. Knighton D. R., Zheng J. H., Ten Eyck L. F., Ashford V. A., Xuong N. H., Taylor S. S., Sowadski J. M. Crystal structure of the catalytic subunit of cyclic adenosine monophosphate-dependent protein kinase. Science. 1991 Jul 26;253(5018):407–414. doi: 10.1126/science.1862342. [DOI] [PubMed] [Google Scholar]
  20. Kyte J., Doolittle R. F. A simple method for displaying the hydropathic character of a protein. J Mol Biol. 1982 May 5;157(1):105–132. doi: 10.1016/0022-2836(82)90515-0. [DOI] [PubMed] [Google Scholar]
  21. Lawrie J. S., Kemp G. The presence of a Ca2+ bridge within the gamma chain of human fibrinogen. Biochim Biophys Acta. 1979 Apr 25;577(2):415–423. doi: 10.1016/0005-2795(79)90046-1. [DOI] [PubMed] [Google Scholar]
  22. Leszczynski J. F., Rose G. D. Loops in globular proteins: a novel category of secondary structure. Science. 1986 Nov 14;234(4778):849–855. doi: 10.1126/science.3775366. [DOI] [PubMed] [Google Scholar]
  23. MIHALYI E., GODFREY J. E. Digestion of fibrinogen by trypsin. II. Characterization of the large fragment obtained. Biochim Biophys Acta. 1963 Jan 8;67:90–103. doi: 10.1016/0006-3002(63)91799-2. [DOI] [PubMed] [Google Scholar]
  24. Medved' L. V., Litvinovich S. V., Privalov P. L. Domain organization of the terminal parts in the fibrinogen molecule. FEBS Lett. 1986 Jul 7;202(2):298–302. doi: 10.1016/0014-5793(86)80705-0. [DOI] [PubMed] [Google Scholar]
  25. Mihalyi E. Physicochemical studies of bovine fibrinogen. 3. Optical rotation of the native and denatured molecule. Biochim Biophys Acta. 1965 Jul 22;102(2):487–499. doi: 10.1016/0926-6585(65)90139-1. [DOI] [PubMed] [Google Scholar]
  26. Morel Y., Bristow J., Gitelman S. E., Miller W. L. Transcript encoded on the opposite strand of the human steroid 21-hydroxylase/complement component C4 gene locus. Proc Natl Acad Sci U S A. 1989 Sep;86(17):6582–6586. doi: 10.1073/pnas.86.17.6582. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Pan Y., Doolittle R. F. cDNA sequence of a second fibrinogen alpha chain in lamprey: an archetypal version alignable with full-length beta and gamma chains. Proc Natl Acad Sci U S A. 1992 Mar 15;89(6):2066–2070. doi: 10.1073/pnas.89.6.2066. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Privalov P. L., Medved L. V. Domains in the fibrinogen molecule. J Mol Biol. 1982 Aug 25;159(4):665–683. doi: 10.1016/0022-2836(82)90107-3. [DOI] [PubMed] [Google Scholar]
  29. Rippmann F., Taylor W. R., Rothbard J. B., Green N. M. A hypothetical model for the peptide binding domain of hsp70 based on the peptide binding domain of HLA. EMBO J. 1991 May;10(5):1053–1059. doi: 10.1002/j.1460-2075.1991.tb08044.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Schiffer M., Edmundson A. B. Use of helical wheels to represent the structures of proteins and to identify segments with helical potential. Biophys J. 1967 Mar;7(2):121–135. doi: 10.1016/S0006-3495(67)86579-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Schulz G. E. A critical evaluation of methods for prediction of protein secondary structures. Annu Rev Biophys Biophys Chem. 1988;17:1–21. doi: 10.1146/annurev.bb.17.060188.000245. [DOI] [PubMed] [Google Scholar]
  32. St Charles R., Walz D. A., Edwards B. F. The three-dimensional structure of bovine platelet factor 4 at 3.0-A resolution. J Biol Chem. 1989 Feb 5;264(4):2092–2099. [PubMed] [Google Scholar]
  33. Strong D. D., Moore M., Cottrell B. A., Bohonus V. L., Pontes M., Evans B., Riley M., Doolittle R. F. Lamprey fibrinogen gamma chain: cloning, cDNA sequencing, and general characterization. Biochemistry. 1985 Jan 1;24(1):92–101. doi: 10.1021/bi00322a014. [DOI] [PubMed] [Google Scholar]
  34. Váradi A., Scheraga H. A. Localization of segments essential for polymerization and for calcium binding in the gamma-chain of human fibrinogen. Biochemistry. 1986 Feb 11;25(3):519–528. doi: 10.1021/bi00351a001. [DOI] [PubMed] [Google Scholar]
  35. Watt K. W., Takagi T., Doolittle R. F. Amino acid sequence of the beta chain of human fibrinogen: homology with the gamma chain. Proc Natl Acad Sci U S A. 1978 Apr;75(4):1731–1735. doi: 10.1073/pnas.75.4.1731. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Weis W. I., Kahn R., Fourme R., Drickamer K., Hendrickson W. A. Structure of the calcium-dependent lectin domain from a rat mannose-binding protein determined by MAD phasing. Science. 1991 Dec 13;254(5038):1608–1615. doi: 10.1126/science.1721241. [DOI] [PubMed] [Google Scholar]
  37. Weisel J. W., Stauffacher C. V., Bullitt E., Cohen C. A model for fibrinogen: domains and sequence. Science. 1985 Dec 20;230(4732):1388–1391. doi: 10.1126/science.4071058. [DOI] [PubMed] [Google Scholar]
  38. Williams R. C. Band patterns seen by electron microscopy in ordered arrays of bovine and human fibrinogen and fibrin after negative staining. Proc Natl Acad Sci U S A. 1983 Mar;80(6):1570–1573. doi: 10.1073/pnas.80.6.1570. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Yamazumi K., Doolittle R. F. Photoaffinity labeling of the primary fibrin polymerization site: localization of the label to gamma-chain Tyr-363. Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):2893–2896. doi: 10.1073/pnas.89.7.2893. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Protein Science : A Publication of the Protein Society are provided here courtesy of The Protein Society

RESOURCES