© The Rockefeller University Press, 0022-1007/1997/2/745/ $5.00
The Journal of Experimental Medicine, Volume 185, Number 4, February 17, 1997 745-754
Mapping the Active Site of CD59
Jinghua Yu*,
Ruben Abagyan
,
Shanghong Dong*,
Alexander Gilbert*,
Victor Nussenzweig*, and
Stephen Tomlinson*
From the * Department of Pathology, New York University Medical Center, New York 10016 and
Department of Biochemistry, The Skirball Institute, New York 10016
CD59 is a widely distributed membrane-bound inhibitor of the cytolytic membrane attack complex (MAC) of complement. This small (77 amino acid) glycoprotein is a member of the Ly6 superfamily of proteins and is important in protecting host cells from the lytic and proinflammatory activity of the MAC. CD59 functions by binding to C8 and/or C9 in the nascent MAC and interfering with C9 membrane insertion and polymerization. We present data obtained from a combination of molecular modeling and mutagenesis techniques, which together indicate that the active site of CD59 is located in the vicinity of a hydrophobic groove on the face of the molecule opposite to a "hydrophobic strip" suggested earlier. In addition, removal of the single N-linked glycosylation site at Asn18 of CD59 resulted in an enhancement of complement inhibitory activity.
Address correspondence to Stephen Tomlinson, New York University Medical Center, Department of Pathology, MSB 127, 550 First Ave., New York, NY 10016. Dr. Dong's present address is Ohio State University, Department of Molecular Genetics, Biological Science Building, 484 West 12th St., Columbus, OH 43210.
1Abbreviations used in this paper: CHO, Chinese hamster ovary cells; GPI, glycosylphosphatidylinositol; MAC, membrane attack complex; NHS, normal human serum.

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