title: Complement regulation at the molecular level: the structure of decay-accelerating factor.
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 A 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.
authors.affiliation: Laboratory of Molecular Biophysics and Glycobiology Institute, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, England.
authors.forename: P
authors.initials: P
authors.lastname: Lukacik
authors.forename: P
authors.initials: P
authors.lastname: Roversi
authors.forename: J
authors.initials: J
authors.lastname: White
authors.forename: D
authors.initials: D
authors.lastname: Esser
authors.forename: G P
authors.initials: GP
authors.lastname: Smith
authors.forename: J
authors.initials: J
authors.lastname: Billington
authors.forename: P A
authors.initials: PA
authors.lastname: Williams
authors.forename: P M
authors.initials: PM
authors.lastname: Rudd
authors.forename: M R
authors.initials: MR
authors.lastname: Wormald
authors.forename: D J
authors.initials: DJ
authors.lastname: Harvey
authors.forename: M D M
authors.initials: MD
authors.lastname: Crispin
authors.forename: C M
authors.initials: CM
authors.lastname: Radcliffe
authors.forename: R A
authors.initials: RA
authors.lastname: Dwek
authors.forename: D J
authors.initials: DJ
authors.lastname: Evans
authors.forename: B P
authors.initials: BP
authors.lastname: Morgan
authors.forename: R A G
authors.initials: RA
authors.lastname: Smith
authors.forename: S M
authors.initials: SM
authors.lastname: Lea
mesh_terms: D018958:CD55 Antigens / Q000737:chemistry*; D003165:Complement System Proteins / Q000502:physiology; D003460:Crystallization; D006031:Glycosylation; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D020449:Repetitive Sequences, Amino Acid; D012996:Solutions; D014841:von Willebrand Factor / Q000737:chemistry
chemical_list: D018958:CD55 Antigens; D012996:Solutions; D014841:von Willebrand Factor; D003165:Complement System Proteins