Open AccessComplement regulation at the molecular level: The structure of decay-accelerating factor
Author(s) -
Petra Lukacik,
Pietro Roversi,
Jessica F White,
D. Esser,
Geoffrey Smith,
J. Billington,
Pamela A. Williams,
Pauline M. Rudd,
Mark R. Wormald,
David J. Harvey,
Max Crispin,
Catherine M. Radcliffe,
Raymond A. Dwek,
David J. Evans,
B. Paul Morgan,
Richard A. Smith,
Susan M. Lea
Publication year - 2004
Publication title -
proceedings of the national academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0307200101
Subject(s) - decay accelerating factor , complement system , c3 convertase , complement (music) , chemistry , factor h , linker , complement membrane attack complex , regulator , biophysics , lysis , glycan , molecule , ultracentrifuge , alternative complement pathway , crystallography , biochemistry , biology , glycoprotein , genetics , gene , computer science , antibody , organic chemistry , operating system , phenotype , complementation
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.
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