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. 1997 Sep 1;326(Pt 2):321–327. doi: 10.1042/bj3260321

The human complement regulatory factor-H-like protein 1, which represents a truncated form of factor H, displays cell-attachment activity.

J Hellwage 1, S Kühn 1, P F Zipfel 1
PMCID: PMC1218672  PMID: 9291099

Abstract

Complement factor H (FH) and factor-H-like protein 1 (FHL-1) are human plasma proteins with regulatory functions in the alternative pathway of complement activation. FH and FHL-1 are organized in repetitive elements termed short consensus repeats (SCRs) and the seven SCRs of FHL-1 are identical with the N-terminal domain of the 20 SCRs of FH. The fourth SCR of both proteins (SCR 4) includes the sequence Arg-Gly-Asp (RGD), a motif that is responsible for the major adhesive activity of matrix proteins like fibronectin. A synthetic hexapeptide with the sequence ERGDAV derived from the RGD domain of FH/FHL-1 interferes with cell attachment to a fibronectin matrix. Although the identical motif is present in both FH and FHL-1, only FHL-1 acts as a matrix for cell spreading and attachment, thus the two proteins differ in function. The adhesive activity of FHL-1 is localized to the RGD-containing SCR 4 by the use of recombinant fragments. All three analysed anchorage-dependent cell lines (CCl64, C32 and MRC-5) adhere to an FHL-1 matrix. The use of synthetic peptides in competition assays, on either FHL-1-derived or fibronectin matrices, shows that the cellular receptors binding to the FH/FHL-1-derived RGD motif are related to or identical with integrin receptors which interact with fibronectin. The identification of a functional adhesive domain in the FH/FHL-1 sequence demonstrates, at least for FHL-1, a role in cell attachment and adhesion.

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Selected References

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  1. Alsenz J., Lambris J. D., Schulz T. F., Dierich M. P. Localization of the complement-component-C3b-binding site and the cofactor activity for factor I in the 38kDa tryptic fragment of factor H. Biochem J. 1984 Dec 1;224(2):389–398. doi: 10.1042/bj2240389. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Aota S., Nagai T., Yamada K. M. Characterization of regions of fibronectin besides the arginine-glycine-aspartic acid sequence required for adhesive function of the cell-binding domain using site-directed mutagenesis. J Biol Chem. 1991 Aug 25;266(24):15938–15943. [PubMed] [Google Scholar]
  3. Avery V. M., Gordon D. L. Characterization of factor H binding to human polymorphonuclear leukocytes. J Immunol. 1993 Nov 15;151(10):5545–5553. [PubMed] [Google Scholar]
  4. Barlow P. N., Norman D. G., Steinkasserer A., Horne T. J., Pearce J., Driscoll P. C., Sim R. B., Campbell I. D. Solution structure of the fifth repeat of factor H: a second example of the complement control protein module. Biochemistry. 1992 Apr 14;31(14):3626–3634. doi: 10.1021/bi00129a011. [DOI] [PubMed] [Google Scholar]
  5. Barlow P. N., Steinkasserer A., Norman D. G., Kieffer B., Wiles A. P., Sim R. B., Campbell I. D. Solution structure of a pair of complement modules by nuclear magnetic resonance. J Mol Biol. 1993 Jul 5;232(1):268–284. doi: 10.1006/jmbi.1993.1381. [DOI] [PubMed] [Google Scholar]
  6. Becherer J. D., Alsenz J., Servis C., Myones B. L., Lambris J. D. Cell surface proteins reacting with activated complement components. Complement Inflamm. 1989;6(3):142–165. doi: 10.1159/000463091. [DOI] [PubMed] [Google Scholar]
  7. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1006/abio.1976.9999. [DOI] [PubMed] [Google Scholar]
  8. Dahmen A., Kaidoh T., Zipfel P. F., Gigli I. Cloning and characterization of a cDNA representing a putative complement-regulatory plasma protein from barred sand bass (Parablax neblifer). Biochem J. 1994 Jul 15;301(Pt 2):391–397. doi: 10.1042/bj3010391. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. DiScipio R. G. Ultrastructures and interactions of complement factors H and I. J Immunol. 1992 Oct 15;149(8):2592–2599. [PubMed] [Google Scholar]
  10. Gordon D. L., Kaufman R. M., Blackmore T. K., Kwong J., Lublin D. M. Identification of complement regulatory domains in human factor H. J Immunol. 1995 Jul 1;155(1):348–356. [PubMed] [Google Scholar]
  11. Hayman E. G., Pierschbacher M. D., Ruoslahti E. Detachment of cells from culture substrate by soluble fibronectin peptides. J Cell Biol. 1985 Jun;100(6):1948–1954. doi: 10.1083/jcb.100.6.1948. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hochuli E., Döbeli H., Schacher A. New metal chelate adsorbent selective for proteins and peptides containing neighbouring histidine residues. J Chromatogr. 1987 Dec 18;411:177–184. doi: 10.1016/s0021-9673(00)93969-4. [DOI] [PubMed] [Google Scholar]
  13. Hynes R. O. Integrins: a family of cell surface receptors. Cell. 1987 Feb 27;48(4):549–554. doi: 10.1016/0092-8674(87)90233-9. [DOI] [PubMed] [Google Scholar]
  14. Hynes R. O. Integrins: versatility, modulation, and signaling in cell adhesion. Cell. 1992 Apr 3;69(1):11–25. doi: 10.1016/0092-8674(92)90115-s. [DOI] [PubMed] [Google Scholar]
  15. Iferroudjene D., Schouft M. T., Lemercier C., Gilbert D., Fontaine M. Evidence for an active hydrophobic form of factor H that is able to induce secretion of interleukin 1-beta or by human monocytes. Eur J Immunol. 1991 Apr;21(4):967–972. doi: 10.1002/eji.1830210416. [DOI] [PubMed] [Google Scholar]
  16. Kristensen T., Tack B. F. Murine protein H is comprised of 20 repeating units, 61 amino acids in length. Proc Natl Acad Sci U S A. 1986 Jun;83(11):3963–3967. doi: 10.1073/pnas.83.11.3963. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kyhse-Andersen J. Electroblotting of multiple gels: a simple apparatus without buffer tank for rapid transfer of proteins from polyacrylamide to nitrocellulose. J Biochem Biophys Methods. 1984 Dec;10(3-4):203–209. doi: 10.1016/0165-022x(84)90040-x. [DOI] [PubMed] [Google Scholar]
  18. Kühn S., Skerka C., Zipfel P. F. Mapping of the complement regulatory domains in the human factor H-like protein 1 and in factor H1. J Immunol. 1995 Dec 15;155(12):5663–5670. [PubMed] [Google Scholar]
  19. Kühn S., Zipfel P. F. Mapping of the domains required for decay acceleration activity of the human factor H-like protein 1 and factor H. Eur J Immunol. 1996 Oct;26(10):2383–2387. doi: 10.1002/eji.1830261017. [DOI] [PubMed] [Google Scholar]
  20. Kühn S., Zipfel P. F. The baculovirus expression vector pBSV-8His directs secretion of histidine-tagged proteins. Gene. 1995 Sep 11;162(2):225–229. doi: 10.1016/0378-1119(95)00360-i. [DOI] [PubMed] [Google Scholar]
  21. Lambris J. D., Ross G. D. Characterization of the lymphocyte membrane receptor for factor H (beta 1H-globulin) with an antibody to anti-factor H idiotype. J Exp Med. 1982 May 1;155(5):1400–1411. doi: 10.1084/jem.155.5.1400. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Loftus J. C., Smith J. W., Ginsberg M. H. Integrin-mediated cell adhesion: the extracellular face. J Biol Chem. 1994 Oct 14;269(41):25235–25238. [PubMed] [Google Scholar]
  23. Meri S., Pangburn M. K. Regulation of alternative pathway complement activation by glycosaminoglycans: specificity of the polyanion binding site on factor H. Biochem Biophys Res Commun. 1994 Jan 14;198(1):52–59. doi: 10.1006/bbrc.1994.1008. [DOI] [PubMed] [Google Scholar]
  24. Misasi R., Huemer H. P., Schwaeble W., Sölder E., Larcher C., Dierich M. P. Human complement factor H: an additional gene product of 43 kDa isolated from human plasma shows cofactor activity for the cleavage of the third component of complement. Eur J Immunol. 1989 Sep;19(9):1765–1768. doi: 10.1002/eji.1830190936. [DOI] [PubMed] [Google Scholar]
  25. Norman D. G., Barlow P. N., Baron M., Day A. J., Sim R. B., Campbell I. D. Three-dimensional structure of a complement control protein module in solution. J Mol Biol. 1991 Jun 20;219(4):717–725. doi: 10.1016/0022-2836(91)90666-t. [DOI] [PubMed] [Google Scholar]
  26. Ohtsuka H., Imamura T., Matsushita M., Tanase S., Okada H., Ogawa M., Kambara T. Thrombin generates monocyte chemotactic activity from complement factor H. Immunology. 1993 Sep;80(1):140–145. [PMC free article] [PubMed] [Google Scholar]
  27. Pangburn M. K., Atkinson M. A., Meri S. Localization of the heparin-binding site on complement factor H. J Biol Chem. 1991 Sep 5;266(25):16847–16853. [PubMed] [Google Scholar]
  28. Pierschbacher M. D., Ruoslahti E. Cell attachment activity of fibronectin can be duplicated by small synthetic fragments of the molecule. Nature. 1984 May 3;309(5963):30–33. doi: 10.1038/309030a0. [DOI] [PubMed] [Google Scholar]
  29. Pierschbacher M. D., Ruoslahti E. Influence of stereochemistry of the sequence Arg-Gly-Asp-Xaa on binding specificity in cell adhesion. J Biol Chem. 1987 Dec 25;262(36):17294–17298. [PubMed] [Google Scholar]
  30. Preissner K. T., Jenne D. Structure of vitronectin and its biological role in haemostasis. Thromb Haemost. 1991 Jul 12;66(1):123–132. [PubMed] [Google Scholar]
  31. Pytela R., Pierschbacher M. D., Argraves S., Suzuki S., Ruoslahti E. Arginine-glycine-aspartic acid adhesion receptors. Methods Enzymol. 1987;144:475–489. doi: 10.1016/0076-6879(87)44196-7. [DOI] [PubMed] [Google Scholar]
  32. Ripoche J., Erdei A., Gilbert D., Al Salihi A., Sim R. B., Fontaine M. Two populations of complement factor H differ in their ability to bind to cell surfaces. Biochem J. 1988 Jul 15;253(2):475–480. doi: 10.1042/bj2530475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Schopf R. E., Hammann K. P., Scheiner O., Lemmel E. M., Dierich M. P. Activation of human monocytes by both human beta 1H and C3b. Immunology. 1982 Jun;46(2):307–312. [PMC free article] [PubMed] [Google Scholar]
  34. Sim R. B., Kölble K., McAleer M. A., Dominguez O., Dee V. M. Genetics and deficiencies of the soluble regulatory proteins of the complement system. Int Rev Immunol. 1993;10(1):65–86. doi: 10.3109/08830189309051172. [DOI] [PubMed] [Google Scholar]
  35. Sjaastad M. D., Angres B., Lewis R. S., Nelson W. J. Feedback regulation of cell-substratum adhesion by integrin-mediated intracellular Ca2+ signaling. Proc Natl Acad Sci U S A. 1994 Aug 16;91(17):8214–8218. doi: 10.1073/pnas.91.17.8214. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Skerka C., Hellwage J., Weber W., Tilkorn A., Buck F., Marti T., Kampen E., Beisiegel U., Zipfel P. F. The human factor H-related protein 4 (FHR-4). A novel short consensus repeat-containing protein is associated with human triglyceride-rich lipoproteins. J Biol Chem. 1997 Feb 28;272(9):5627–5634. doi: 10.1074/jbc.272.9.5627. [DOI] [PubMed] [Google Scholar]
  37. Taniguchi-Sidle A., Isenman D. E. Mutagenesis of the Arg-Gly-Asp triplet in human complement component C3 does not abolish binding of iC3b to the leukocyte integrin complement receptor type III (CR3, CD11b/CD18). J Biol Chem. 1992 Jan 5;267(1):635–643. [PubMed] [Google Scholar]
  38. Wright S. D., Weitz J. I., Huang A. J., Levin S. M., Silverstein S. C., Loike J. D. Complement receptor type three (CD11b/CD18) of human polymorphonuclear leukocytes recognizes fibrinogen. Proc Natl Acad Sci U S A. 1988 Oct;85(20):7734–7738. doi: 10.1073/pnas.85.20.7734. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Zhao Y., Sane D. C. The cell attachment and spreading activity of vitronectin is dependent on the Arg-Gly-Asp sequence. Analysis by construction of RGD and domain deletion mutants. Biochem Biophys Res Commun. 1993 Apr 30;192(2):575–582. doi: 10.1006/bbrc.1993.1454. [DOI] [PubMed] [Google Scholar]
  40. Zipfel P. F., Skerka C. Complement factor H and related proteins: an expanding family of complement-regulatory proteins? Immunol Today. 1994 Mar;15(3):121–126. doi: 10.1016/0167-5699(94)90155-4. [DOI] [PubMed] [Google Scholar]

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