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Related Experiment Videos

Mapping the active site of CD59

J Yu1, R Abagyan, S Dong

  • 1Department of Pathology, New York University Medical Center, New York 10016, USA.

The Journal of Experimental Medicine
|February 17, 1997
PubMed
Summary

CD59 protein inhibits the membrane attack complex (MAC) of complement. Molecular modeling and mutagenesis reveal CD59

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Area of Science:

  • Immunology
  • Molecular Biology
  • Structural Biology

Background:

  • CD59 is a crucial complement inhibitor protecting host cells from MAC-mediated damage.
  • It belongs to the Ly6 superfamily and regulates complement's lytic and inflammatory functions.

Purpose of the Study:

  • To elucidate the active site of CD59 using molecular modeling and mutagenesis.
  • To investigate the role of glycosylation in CD59's complement inhibitory activity.

Main Methods:

  • Molecular modeling techniques were employed to analyze CD59 structure.
  • Site-directed mutagenesis was used to identify key residues and functional sites.
  • Complement inhibitory activity was assessed after modifying the glycosylation site.

Main Results:

  • The active site of CD59 is localized near a hydrophobic groove, distinct from previously proposed regions.
  • Removal of the N-linked glycosylation site at Asn18 enhanced CD59's complement inhibitory function.
  • Mutagenesis data refined the understanding of CD59's interaction with C8 and C9.

Conclusions:

  • The study precisely maps the CD59 active site, advancing our understanding of complement regulation.
  • Glycosylation at Asn18 negatively impacts CD59's inhibitory efficacy.
  • These findings offer insights for developing targeted therapies involving the complement system.

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