Role of a disulfide-bonded peptide loop within human complement C9 in the species-selectivity of complement inhibitor CD59

Biochemistry
T HüslerP J Sims

Abstract

CD59 antigen is a membrane glycoprotein that inhibits the activity of the C9 component of the C5b-9 membrane attack complex (MAC), thereby protecting human cells from lysis by human complement. The complement-inhibitory activity of CD59 is species-selective, and is most effective toward C9 derived from human or other primate plasma. The species-selective activity of CD59 was recently used to map the segment of human C9 that is recognized by this MAC inhibitor, using recombinant rabbit/human C9 chimeras that retain lytic function within the MAC [Husler, T., Lockert, D. H., Kaufman, K. M., Sodetz, J. M., & Sims, P. J. (1995) J. Biol. Chem. 270,3483-3486]. These experiments suggested that the CD59 recognition domain was contained between residues 334 and 415 in human C9. By analyzing the species-selective lytic activity of recombinant C9 with chimeric substitutions internal to this segment, we now demonstrate that the site in human C9 uniquely recognized by CD59 is centered on those residues contained between C9 Cys359/Cys384, with an additional contribution by residues C-terminal to this segment. Consistent with its role as a CD59 recognition domain, CD59 specifically bound a human C9-derived peptide corresponding to residues 359...Continue Reading

Citations

Mar 17, 2010·Cellular & Molecular Immunology·Qigui YuXuebin Qin
Oct 24, 2003·Infection and Immunity·Jiusheng DengZvi Fishelson
Dec 23, 1999·Current Biology : CB·C P Ponting
Jul 28, 2004·International Journal of Radiation Oncology, Biology, Physics·M Carmen Hernandez, Susan J Knox
Jul 18, 2006·The Journal of Biological Chemistry·Yuxiang HuangStephen Tomlinson
Aug 18, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·Y M QianW C Song
Dec 16, 2018·Nature Communications·Anaïs MennyDoryen Bubeck

❮ Previous
Next ❯

Related Concepts

Related Feeds

Alternative Complement Pathway

The Alternative Complement Pathway is part of the innate immune system, and activation generates membrane attack complexes that kill pathogenic cells. Discover the latest research on the Alternative Complement Pathway.