Identity of the residues responsible for the species-restricted complement inhibitory function of human CD59.

The Journal of Biological Chemistry
X J ZhaoP J Sims

Abstract

The membrane-anchored glycoprotein CD59 inhibits assembly of the C5b-9 membrane attack complex (MAC) of human complement. This inhibitory function of CD59 is markedly selective for MAC assembled from human complement components C8 and C9, and CD59 shows little inhibitory function toward MAC assembled from rabbit and many other non-primate species. We have used this species selectivity of CD59 to identify the residues regulating its complement inhibitory function: cDNA of rabbit CD59 was cloned and used to express human/rabbit CD59 chimeras in murine SV-T2 cells. Plasma membrane expression of each CD59 chimera was quantified by use of a 5'-TAG peptide epitope, and each construct was tested for its ability to inhibit assembly of functional MAC from human versus rabbit C8 and C9. These experiments revealed that the species selectivity of CD59 is entirely determined by sequence contained between residues 42 and 58 of the human CD59 polypeptide, whereas chimeric substitution outside this peptide segment has little effect on the MAC inhibitory function of CD59. Substitution of human CD59 residues 42-58 into rabbit CD59 resulted in a molecule that was functionally indistinguishable from native human CD59, whereas the complementary con...Continue Reading

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Citations

Nov 4, 2000·Biochimica Et Biophysica Acta·S F SchreckJ M Sodetz
Mar 17, 2010·Cellular & Molecular Immunology·Qigui YuXuebin Qin
Nov 16, 2004·Nature Structural & Molecular Biology·Kara S GiddingsRodney K Tweten
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Jun 9, 2020·FEBS Letters·Palak AgrawalArvind Sahu
Nov 26, 1999·Biochimica Et Biophysica Acta·M Tomita

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