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Mapping the active site of CD59.

ABSTRACT: 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.

SUBMITTER: Yu J

PROVIDER: S-EPMC2196154 | biostudies-literature | 1997 Feb

REPOSITORIES: biostudies-literature

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Mapping the active site of CD59.

Yu J J Abagyan R R Dong S S Gilbert A A Nussenzweig V V Tomlinson S S

The Journal of experimental medicine 19970201 4

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 mutag ...[more]

PMID: 9034152

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Mutational analysis of the active site and antibody epitopes of the complement-inhibitory glycoprotein, CD59.

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