ELIMINATION OF POTENTIAL SITES OF GLYCOSYLATION FAILS TO ABROGATE COMPLEMENT REGULATORY FUNCTION OF CELL-SURFACE CD59

CD59 is a glycosylphosphatidylinositol-anchored membrane glycoprotein that serves as the principle cellular inhibitor of the C5b-9 membrane attack complex (MAC) of human complement, Approximately 50% of the tot al apparent mass of CD59 is attributable to glycosylation of a single Asn (Asn(18)), The deduced amino acid sequences of CD59 homologues ide ntified in Old and New World primates as well as in rat reveal that th e motif for N-linked glycosylation at the residue corresponding to Asn (18) of human CD59 is invariably conserved, despite considerable seque nce divergence elsewhere in the protein, Such conservation suggests th at the post translational modification at Asn(18) has importance for e ither expression or normal function of CD59 at the cell surface, In th is study, we specifically examined how deletion or transposition of th e site of N-linked glycosylation in the CD59 polypeptide affects its M AC inhibitory function. Our data demonstrate that the inhibitory poten cy of CD59 is unaffected when glycosylation is transposed from Asn(18) to another site in the polypeptide. Furthermore, we show that CD59 re tains normal MAC regulatory function when mutated to eliminate all pot ential sites for N-linked glycosylation, These data suggest that the M AC inhibitory function of CD59 is entirely provided by residues expose d at the surface of the core polypeptide and that this core structure is not influenced by glycosylation at Asn(18).