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. 1987 Apr;84(7):1965–1968. doi: 10.1073/pnas.84.7.1965

C3bi receptor (complement receptor type 3) recognizes a region of complement protein C3 containing the sequence Arg-Gly-Asp.

S D Wright, P A Reddy, M T Jong, B W Erickson
PMCID: PMC304562  PMID: 3550803

Abstract

Human phagocytes express a receptor termed complement receptor type 3 (CR3) that recognizes the complement protein fragment C3bi. We show here that CR3 recognizes a region of C3 that contains the sequence Arg-Gly-Asp (RGD). CR3 is down-modulated upon spreading of macrophages on surfaces coated with a synthetic 21-residue peptide from C3 (residues 1383-1403). This peptide was also attached to erythrocytes by coupling myristic acid to its amino terminus and allowing the myristoylated peptide to bind to erythrocytes through hydrophobic interactions. Erythrocytes coated with this RGD-containing segment of C3 were bound by macrophages, and binding could be blocked by specific monoclonal antibodies against CR3. Since CR3 recognizes a peptide sequence that contains the RGD triplet, it appears to be a member of a larger family of adhesion-promoting receptors that recognize RGD-containing proteins. However, since CR3 does not recognize a hexapeptide containing RGD, we presume that residues beyond the RGD triplet contribute to binding. We have compared the RGD-containing region of fibronectin and vitronectin, proteins known to be recognized by means of their RGD-containing regions, with those in human and murine C3. A striking homology is observed over an approximately equal to 50 amino acid sequence present in all four proteins. We suggest that this extended region of homology contains a structure recognized by adhesion-promoting receptors.

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1965

Selected References

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  1. Belt K. T., Carroll M. C., Porter R. R. The structural basis of the multiple forms of human complement component C4. Cell. 1984 Apr;36(4):907–914. doi: 10.1016/0092-8674(84)90040-0. [DOI] [PubMed] [Google Scholar]
  2. Bohnsack J. F., Kleinman H. K., Takahashi T., O'Shea J. J., Brown E. J. Connective tissue proteins and phagocytic cell function. Laminin enhances complement and Fc-mediated phagocytosis by cultured human macrophages. J Exp Med. 1985 May 1;161(5):912–923. doi: 10.1084/jem.161.5.912. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cheresh D. A., Klier F. G. Disialoganglioside GD2 distributes preferentially into substrate-associated microprocesses on human melanoma cells during their attachment to fibronectin. J Cell Biol. 1986 May;102(5):1887–1897. doi: 10.1083/jcb.102.5.1887. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cross F. R., Garber E. A., Pellman D., Hanafusa H. A short sequence in the p60src N terminus is required for p60src myristylation and membrane association and for cell transformation. Mol Cell Biol. 1984 Sep;4(9):1834–1842. doi: 10.1128/mcb.4.9.1834. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Fleit H. B., Wright S. D., Unkeless J. C. Human neutrophil Fc gamma receptor distribution and structure. Proc Natl Acad Sci U S A. 1982 May;79(10):3275–3279. doi: 10.1073/pnas.79.10.3275. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Horwitz A., Duggan K., Greggs R., Decker C., Buck C. The cell substrate attachment (CSAT) antigen has properties of a receptor for laminin and fibronectin. J Cell Biol. 1985 Dec;101(6):2134–2144. doi: 10.1083/jcb.101.6.2134. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Kornblihtt A. R., Vibe-Pedersen K., Baralle F. E. Human fibronectin: cell specific alternative mRNA splicing generates polypeptide chains differing in the number of internal repeats. Nucleic Acids Res. 1984 Jul 25;12(14):5853–5868. doi: 10.1093/nar/12.14.5853. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Lanier L. L., Arnaout M. A., Schwarting R., Warner N. L., Ross G. D. p150/95, Third member of the LFA-1/CR3 polypeptide family identified by anti-Leu M5 monoclonal antibody. Eur J Immunol. 1985 Jul;15(7):713–718. doi: 10.1002/eji.1830150714. [DOI] [PubMed] [Google Scholar]
  9. Lundwall A., Wetsel R. A., Domdey H., Tack B. F., Fey G. H. Structure of murine complement component C3. I. Nucleotide sequence of cloned complementary and genomic DNA coding for the beta chain. J Biol Chem. 1984 Nov 25;259(22):13851–13856. [PubMed] [Google Scholar]
  10. Pytela R., Pierschbacher M. D., Ginsberg M. H., Plow E. F., Ruoslahti E. Platelet membrane glycoprotein IIb/IIIa: member of a family of Arg-Gly-Asp--specific adhesion receptors. Science. 1986 Mar 28;231(4745):1559–1562. doi: 10.1126/science.2420006. [DOI] [PubMed] [Google Scholar]
  11. Pytela R., Pierschbacher M. D., Ruoslahti E. A 125/115-kDa cell surface receptor specific for vitronectin interacts with the arginine-glycine-aspartic acid adhesion sequence derived from fibronectin. Proc Natl Acad Sci U S A. 1985 Sep;82(17):5766–5770. doi: 10.1073/pnas.82.17.5766. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Pytela R., Pierschbacher M. D., Ruoslahti E. Identification and isolation of a 140 kd cell surface glycoprotein with properties expected of a fibronectin receptor. Cell. 1985 Jan;40(1):191–198. doi: 10.1016/0092-8674(85)90322-8. [DOI] [PubMed] [Google Scholar]
  13. Ruoslahti E., Pierschbacher M. D. Arg-Gly-Asp: a versatile cell recognition signal. Cell. 1986 Feb 28;44(4):517–518. doi: 10.1016/0092-8674(86)90259-x. [DOI] [PubMed] [Google Scholar]
  14. Sanchez-Madrid F., Krensky A. M., Ware C. F., Robbins E., Strominger J. L., Burakoff S. J., Springer T. A. Three distinct antigens associated with human T-lymphocyte-mediated cytolysis: LFA-1, LFA-2, and LFA-3. Proc Natl Acad Sci U S A. 1982 Dec;79(23):7489–7493. doi: 10.1073/pnas.79.23.7489. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Sanchez-Madrid F., Nagy J. A., Robbins E., Simon P., Springer T. A. A human leukocyte differentiation antigen family with distinct alpha-subunits and a common beta-subunit: the lymphocyte function-associated antigen (LFA-1), the C3bi complement receptor (OKM1/Mac-1), and the p150,95 molecule. J Exp Med. 1983 Dec 1;158(6):1785–1803. doi: 10.1084/jem.158.6.1785. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Sepich D. S., Noonan D. J., Ogata R. T. Complete cDNA sequence of the fourth component of murine complement. Proc Natl Acad Sci U S A. 1985 Sep;82(17):5895–5899. doi: 10.1073/pnas.82.17.5895. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Shaw S., Luce G. E., Quinones R., Gress R. E., Springer T. A., Sanders M. E. Two antigen-independent adhesion pathways used by human cytotoxic T-cell clones. Nature. 1986 Sep 18;323(6085):262–264. doi: 10.1038/323262a0. [DOI] [PubMed] [Google Scholar]
  18. Sottrup-Jensen L., Gliemann J., Van Leuven F. Domain structure of human alpha 2-macroglobulin. Characterization of a receptor-binding domain obtained by digestion with papain. FEBS Lett. 1986 Sep 1;205(1):20–24. doi: 10.1016/0014-5793(86)80857-2. [DOI] [PubMed] [Google Scholar]
  19. Sottrup-Jensen L., Stepanik T. M., Kristensen T., Lønblad P. B., Jones C. M., Wierzbicki D. M., Magnusson S., Domdey H., Wetsel R. A., Lundwall A. Common evolutionary origin of alpha 2-macroglobulin and complement components C3 and C4. Proc Natl Acad Sci U S A. 1985 Jan;82(1):9–13. doi: 10.1073/pnas.82.1.9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Sottrup-Jensen L., Stepanik T. M., Kristensen T., Wierzbicki D. M., Jones C. M., Lønblad P. B., Magnusson S., Petersen T. E. Primary structure of human alpha 2-macroglobulin. V. The complete structure. J Biol Chem. 1984 Jul 10;259(13):8318–8327. [PubMed] [Google Scholar]
  21. Suzuki S., Oldberg A., Hayman E. G., Pierschbacher M. D., Ruoslahti E. Complete amino acid sequence of human vitronectin deduced from cDNA. Similarity of cell attachment sites in vitronectin and fibronectin. EMBO J. 1985 Oct;4(10):2519–2524. doi: 10.1002/j.1460-2075.1985.tb03965.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Tamkun J. W., DeSimone D. W., Fonda D., Patel R. S., Buck C., Horwitz A. F., Hynes R. O. Structure of integrin, a glycoprotein involved in the transmembrane linkage between fibronectin and actin. Cell. 1986 Jul 18;46(2):271–282. doi: 10.1016/0092-8674(86)90744-0. [DOI] [PubMed] [Google Scholar]
  23. Wright S. D., Jong M. T. Adhesion-promoting receptors on human macrophages recognize Escherichia coli by binding to lipopolysaccharide. J Exp Med. 1986 Dec 1;164(6):1876–1888. doi: 10.1084/jem.164.6.1876. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Wright S. D., Meyer B. C. Fibronectin receptor of human macrophages recognizes the sequence Arg-Gly-Asp-Ser. J Exp Med. 1985 Aug 1;162(2):762–767. doi: 10.1084/jem.162.2.762. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Wright S. D., Rao P. E., Van Voorhis W. C., Craigmyle L. S., Iida K., Talle M. A., Westberg E. F., Goldstein G., Silverstein S. C. Identification of the C3bi receptor of human monocytes and macrophages by using monoclonal antibodies. Proc Natl Acad Sci U S A. 1983 Sep;80(18):5699–5703. doi: 10.1073/pnas.80.18.5699. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Wright S. D., Silverstein S. C. Tumor-promoting phorbol esters stimulate C3b and C3b' receptor-mediated phagocytosis in cultured human monocytes. J Exp Med. 1982 Oct 1;156(4):1149–1164. doi: 10.1084/jem.156.4.1149. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. de Bruijn M. H., Fey G. H. Human complement component C3: cDNA coding sequence and derived primary structure. Proc Natl Acad Sci U S A. 1985 Feb;82(3):708–712. doi: 10.1073/pnas.82.3.708. [DOI] [PMC free article] [PubMed] [Google Scholar]

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