Complement regulation at the molecular level: The structure of decay-accelerating factor

P Lukacik, P Roversi, J White, D Esser, GP Smith, J Billington, PA Williams, PM Rudd, MR Wormald, DJ Harvey, MDM Crispin, CM Radcliffe, RA Dwek, DJ Evans, BP Morgan, RAG Smith, SM Lea*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

89 Citations (Scopus)

Abstract

The human complement regulator CD55 is a key molecule protecting self-cells from complement-mediated lysis. X-ray diffraction and analytical ultracentrifugation data reveal a rod-like arrangement of four short consensus repeat (SCR) domains in both the crystal and solution. The stalk linking the four SCR domains to the glycosylphosphatidylinositol anchor is extended by the addition of 11 highly charged O-glycans and positions the domains an estimated 177 Angstrom above the membrane. Mutation mapping and hydrophobic potential analysis suggest that the interaction with the convertase, and thus complement regulation, depends on the burial of a hydrophobic patch centered on the linker between SCR domains 2 and 3.

Original languageEnglish
Pages (from-to)1279-1284
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number5
DOIs
Publication statusPublished - 3 Feb 2004

Keywords

  • CD55
  • complement regulator
  • pathogen receptor
  • glycoprotein
  • OVINE SUBMAXILLARY MUCIN
  • O-LINKED GLYCOPROTEINS
  • GLYCOSYLATION SITES
  • CONTROL PROTEIN
  • RECEPTOR CD97
  • C3 CONVERTASE
  • LIGAND CD55
  • A DOMAIN
  • FACTOR-H
  • BINDING

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