Mapping the active site of CD59.
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.
Yu
J
J
Department of Pathology, New York University Medical Center, New York 10016, USA.
Abagyan
R
R
Dong
S
S
Gilbert
A
A
Nussenzweig
V
V
Tomlinson
S
S
D000595:Amino Acid Sequence; D000818:Animals; D000954:Antigens, Surface / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D018957:CD59 Antigens / Q000235:genetics / Q000378:metabolism*; D016466:CHO Cells; D050260:Carbohydrate Metabolism; D006224:Cricetinae; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D017386:Sequence Homology, Amino Acid
D000954:Antigens, Surface; D018957:CD59 Antigens