Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1991 Apr 15;88(8):3446–3450. doi: 10.1073/pnas.88.8.3446

Three-dimensional structure of human basic fibroblast growth factor, a structural homolog of interleukin 1 beta.

J D Zhang 1, L S Cousens 1, P J Barr 1, S R Sprang 1
PMCID: PMC51464  PMID: 1849658

Abstract

The three-dimensional structure of the 146-residue form of human basic fibroblast growth factor (bFGF), expressed as a recombinant protein in yeast, has been determined by x-ray crystallography to a resolution of 1.8 A. bFGF is composed entirely of beta-sheet structure, comprising a three-fold repeat of a four-stranded antiparallel beta-meander. The topology of bFGF is identical to that of interleukin 1 beta, showing that although the two proteins share only 10% sequence identity, bFGF, interleukin 1, and their homologs comprise a family of structurally related mitogenic factors. Analysis of the three-dimensional structure in light of functional studies of bFGF suggests that the receptor binding site and the positively charged heparin binding site correspond to adjacent but separate loci on the beta-barrel.

Full text

PDF
3446

Images in this article

3447Image
on p.3447
3448Image
on p.3448
3448Image
on p.3448
3448Image
on p.3448
3449Image
on p.3449
3450Image
on p.3450

Selected References

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

  1. Arakawa T., Hsu Y. R., Schiffer S. G., Tsai L. B., Curless C., Fox G. M. Characterization of a cysteine-free analog of recombinant human basic fibroblast growth factor. Biochem Biophys Res Commun. 1989 May 30;161(1):335–341. doi: 10.1016/0006-291x(89)91601-x. [DOI] [PubMed] [Google Scholar]
  2. Baird A., Schubert D., Ling N., Guillemin R. Receptor- and heparin-binding domains of basic fibroblast growth factor. Proc Natl Acad Sci U S A. 1988 Apr;85(7):2324–2328. doi: 10.1073/pnas.85.7.2324. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Barr P. J., Cousens L. S., Lee-Ng C. T., Medina-Selby A., Masiarz F. R., Hallewell R. A., Chamberlain S. H., Bradley J. D., Lee D., Steimer K. S. Expression and processing of biologically active fibroblast growth factors in the yeast Saccharomyces cerevisiae. J Biol Chem. 1988 Nov 5;263(31):16471–16478. [PubMed] [Google Scholar]
  4. Barr P. J., Gibson H. L., Enea V., Arnot D. E., Hollingdale M. R., Nussenzweig V. Expression in yeast of a Plasmodium vivax antigen of potential use in a human malaria vaccine. J Exp Med. 1987 Apr 1;165(4):1160–1171. doi: 10.1084/jem.165.4.1160. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bernstein F. C., Koetzle T. F., Williams G. J., Meyer E. F., Jr, Brice M. D., Rodgers J. R., Kennard O., Shimanouchi T., Tasumi M. The Protein Data Bank: a computer-based archival file for macromolecular structures. J Mol Biol. 1977 May 25;112(3):535–542. doi: 10.1016/s0022-2836(77)80200-3. [DOI] [PubMed] [Google Scholar]
  6. Brünger A. T., Kuriyan J., Karplus M. Crystallographic R factor refinement by molecular dynamics. Science. 1987 Jan 23;235(4787):458–460. doi: 10.1126/science.235.4787.458. [DOI] [PubMed] [Google Scholar]
  7. Burgess W. H., Maciag T. The heparin-binding (fibroblast) growth factor family of proteins. Annu Rev Biochem. 1989;58:575–606. doi: 10.1146/annurev.bi.58.070189.003043. [DOI] [PubMed] [Google Scholar]
  8. Burgess W. H., Shaheen A. M., Ravera M., Jaye M., Donohue P. J., Winkles J. A. Possible dissociation of the heparin-binding and mitogenic activities of heparin-binding (acidic fibroblast) growth factor-1 from its receptor-binding activities by site-directed mutagenesis of a single lysine residue. J Cell Biol. 1990 Nov;111(5 Pt 1):2129–2138. doi: 10.1083/jcb.111.5.2129. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dionne C. A., Crumley G., Bellot F., Kaplow J. M., Searfoss G., Ruta M., Burgess W. H., Jaye M., Schlessinger J. Cloning and expression of two distinct high-affinity receptors cross-reacting with acidic and basic fibroblast growth factors. EMBO J. 1990 Sep;9(9):2685–2692. doi: 10.1002/j.1460-2075.1990.tb07454.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Eck M. J., Sprang S. R. The structure of tumor necrosis factor-alpha at 2.6 A resolution. Implications for receptor binding. J Biol Chem. 1989 Oct 15;264(29):17595–17605. doi: 10.2210/pdb1tnf/pdb. [DOI] [PubMed] [Google Scholar]
  11. Eriksson A. E., Cousens L. S., Weaver L. H., Matthews B. W. Three-dimensional structure of human basic fibroblast growth factor. Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3441–3445. doi: 10.1073/pnas.88.8.3441. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Esch F., Baird A., Ling N., Ueno N., Hill F., Denoroy L., Klepper R., Gospodarowicz D., Böhlen P., Guillemin R. Primary structure of bovine pituitary basic fibroblast growth factor (FGF) and comparison with the amino-terminal sequence of bovine brain acidic FGF. Proc Natl Acad Sci U S A. 1985 Oct;82(19):6507–6511. doi: 10.1073/pnas.82.19.6507. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Feige J. J., Baird A. Basic fibroblast growth factor is a substrate for protein phosphorylation and is phosphorylated by capillary endothelial cells in culture. Proc Natl Acad Sci U S A. 1989 May;86(9):3174–3178. doi: 10.1073/pnas.86.9.3174. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Finch P. W., Rubin J. S., Miki T., Ron D., Aaronson S. A. Human KGF is FGF-related with properties of a paracrine effector of epithelial cell growth. Science. 1989 Aug 18;245(4919):752–755. doi: 10.1126/science.2475908. [DOI] [PubMed] [Google Scholar]
  15. Finzel B. C., Clancy L. L., Holland D. R., Muchmore S. W., Watenpaugh K. D., Einspahr H. M. Crystal structure of recombinant human interleukin-1 beta at 2.0 A resolution. J Mol Biol. 1989 Oct 20;209(4):779–791. doi: 10.1016/0022-2836(89)90606-2. [DOI] [PubMed] [Google Scholar]
  16. Fox G. M., Schiffer S. G., Rohde M. F., Tsai L. B., Banks A. R., Arakawa T. Production, biological activity, and structure of recombinant basic fibroblast growth factor and an analog with cysteine replaced by serine. J Biol Chem. 1988 Dec 5;263(34):18452–18458. [PubMed] [Google Scholar]
  17. Gimenez-Gallego G., Rodkey J., Bennett C., Rios-Candelore M., DiSalvo J., Thomas K. Brain-derived acidic fibroblast growth factor: complete amino acid sequence and homologies. Science. 1985 Dec 20;230(4732):1385–1388. doi: 10.1126/science.4071057. [DOI] [PubMed] [Google Scholar]
  18. Gospodarowicz D., Cheng J. Heparin protects basic and acidic FGF from inactivation. J Cell Physiol. 1986 Sep;128(3):475–484. doi: 10.1002/jcp.1041280317. [DOI] [PubMed] [Google Scholar]
  19. Greer J. Comparative model-building of the mammalian serine proteases. J Mol Biol. 1981 Dec 25;153(4):1027–1042. doi: 10.1016/0022-2836(81)90465-4. [DOI] [PubMed] [Google Scholar]
  20. Greer J. Comparative modeling methods: application to the family of the mammalian serine proteases. Proteins. 1990;7(4):317–334. doi: 10.1002/prot.340070404. [DOI] [PubMed] [Google Scholar]
  21. Harper J. W., Lobb R. R. Reductive methylation of lysine residues in acidic fibroblast growth factor: effect on mitogenic activity and heparin affinity. Biochemistry. 1988 Jan 26;27(2):671–678. doi: 10.1021/bi00402a027. [DOI] [PubMed] [Google Scholar]
  22. Howard A. J., Nielsen C., Xuong N. H. Software for a diffractometer with multiwire area detector. Methods Enzymol. 1985;114:452–472. doi: 10.1016/0076-6879(85)14030-9. [DOI] [PubMed] [Google Scholar]
  23. Jones T. A., Thirup S. Using known substructures in protein model building and crystallography. EMBO J. 1986 Apr;5(4):819–822. doi: 10.1002/j.1460-2075.1986.tb04287.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Klagsbrun M., Smith S., Sullivan R., Shing Y., Davidson S., Smith J. A., Sasse J. Multiple forms of basic fibroblast growth factor: amino-terminal cleavages by tumor cell- and brain cell-derived acid proteinases. Proc Natl Acad Sci U S A. 1987 Apr;84(7):1839–1843. doi: 10.1073/pnas.84.7.1839. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Kurokawa M., Doctrow S. R., Klagsbrun M. Neutralizing antibodies inhibit the binding of basic fibroblast growth factor to its receptor but not to heparin. J Biol Chem. 1989 May 5;264(13):7686–7691. [PubMed] [Google Scholar]
  26. Lee B., Richards F. M. The interpretation of protein structures: estimation of static accessibility. J Mol Biol. 1971 Feb 14;55(3):379–400. doi: 10.1016/0022-2836(71)90324-x. [DOI] [PubMed] [Google Scholar]
  27. Lee P. L., Johnson D. E., Cousens L. S., Fried V. A., Williams L. T. Purification and complementary DNA cloning of a receptor for basic fibroblast growth factor. Science. 1989 Jul 7;245(4913):57–60. doi: 10.1126/science.2544996. [DOI] [PubMed] [Google Scholar]
  28. Lobb R. R., Harper J. W., Fett J. W. Purification of heparin-binding growth factors. Anal Biochem. 1986 Apr;154(1):1–14. doi: 10.1016/0003-2697(86)90487-2. [DOI] [PubMed] [Google Scholar]
  29. Marics I., Adelaide J., Raybaud F., Mattei M. G., Coulier F., Planche J., de Lapeyriere O., Birnbaum D. Characterization of the HST-related FGF.6 gene, a new member of the fibroblast growth factor gene family. Oncogene. 1989 Mar;4(3):335–340. [PubMed] [Google Scholar]
  30. Neufeld G., Gospodarowicz D. Basic and acidic fibroblast growth factors interact with the same cell surface receptors. J Biol Chem. 1986 Apr 25;261(12):5631–5637. [PubMed] [Google Scholar]
  31. Priestle J. P., Schär H. P., Grütter M. G. Crystallographic refinement of interleukin 1 beta at 2.0 A resolution. Proc Natl Acad Sci U S A. 1989 Dec;86(24):9667–9671. doi: 10.1073/pnas.86.24.9667. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Seno M., Sasada R., Iwane M., Sudo K., Kurokawa T., Ito K., Igarashi K. Stabilizing basic fibroblast growth factor using protein engineering. Biochem Biophys Res Commun. 1988 Mar 15;151(2):701–708. doi: 10.1016/s0006-291x(88)80337-1. [DOI] [PubMed] [Google Scholar]
  33. Seno M., Sasada R., Kurokawa T., Igarashi K. Carboxyl-terminal structure of basic fibroblast growth factor significantly contributes to its affinity for heparin. Eur J Biochem. 1990 Mar 10;188(2):239–245. doi: 10.1111/j.1432-1033.1990.tb15395.x. [DOI] [PubMed] [Google Scholar]
  34. Sprang S. R., Acharya K. R., Goldsmith E. J., Stuart D. I., Varvill K., Fletterick R. J., Madsen N. B., Johnson L. N. Structural changes in glycogen phosphorylase induced by phosphorylation. Nature. 1988 Nov 17;336(6196):215–221. doi: 10.1038/336215a0. [DOI] [PubMed] [Google Scholar]
  35. Whitman M., Melton D. A. Growth factors in early embryogenesis. Annu Rev Cell Biol. 1989;5:93–117. doi: 10.1146/annurev.cb.05.110189.000521. [DOI] [PubMed] [Google Scholar]
  36. Zhu X., Komiya H., Chirino A., Faham S., Fox G. M., Arakawa T., Hsu B. T., Rees D. C. Three-dimensional structures of acidic and basic fibroblast growth factors. Science. 1991 Jan 4;251(4989):90–93. doi: 10.1126/science.1702556. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES