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

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.

[1]  J. Kearney,et al.  Probing functional sites on complement protein B with monoclonal antibodies. Evidence for C3b-binding sites on Ba. , 1987, Journal of immunology.

[2]  G. Ball,et al.  Solution structure of a functionally active fragment of decay-accelerating factor , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[3]  B. Morgan.  The Human Complement System in Health and Disease. , 1998 .

[4]  T. Fujita,et al.  Mapping of epitopes, glycosylation sites, and complement regulatory domains in human decay accelerating factor. , 1992, Journal of immunology.

[5]  N Jentoft,et al.  Why are proteins O-glycosylated? , 1990, Trends in biochemical sciences.

[6]  Pauline M Rudd,et al.  An analytical and structural database provides a strategy for sequencing O-glycans from microgram quantities of glycoproteins. , 2002, Analytical biochemistry.

[7]  Y. Edwards,et al.  Identification of the C3b binding site in a recombinant vWF-A domain of complement factor B by surface-enhanced laser desorption-ionisation affinity mass spectrometry and homology modelling: implications for the activity of factor B. , 1999, Journal of molecular biology.

[8]  J. Atkinson,et al.  Structure of the gene for human complement protein decay accelerating factor. , 1990, Journal of immunology.

[9]  K D Cowtan,et al.  Improvement of macromolecular electron-density maps by the simultaneous application of real and reciprocal space constraints. , 1993, Acta crystallographica. Section D, Biological crystallography.

[10]  R. Wallis,et al.  Asymmetry adjacent to the collagen-like domain in rat liver mannose-binding protein. , 1997, The Biochemical journal.

[11]  K. Butenhof,et al.  Effects of glycosylation on the conformation and dynamics of O-linked glycoproteins: carbon-13 NMR studies of ovine submaxillary mucin. , 1989, Biochemistry.

[12]  Raymond A Dwek,et al.  Conformational studies of oligosaccharides and glycopeptides: complementarity of NMR, X-ray crystallography, and molecular modelling. , 2002, Chemical reviews.

[13]  J. García de la Torre,et al.  Calculation of hydrodynamic properties of globular proteins from their atomic-level structure. , 2000, Biophysical journal.

[14]  J. Volanakis.  The human complement system in health and disease , 1998 .

[15]  R. Dwek,et al.  The Glycosylation of the Complement Regulatory Protein, Human Erythrocyte CD59* , 1997, The Journal of Biological Chemistry.

[16]  R. Hintzen,et al.  Expression of the EGF-TM7 receptor CD97 and its ligand CD55 (DAF) in multiple sclerosis , 2002, Journal of Neuroimmunology.

[17]  S. Lea.  Interactions of CD55 with non-complement ligands. , 2001, Biochemical Society transactions.

[18]  K. Murthy,et al.  RETRACTED: Crystal Structure of a Complement Control Protein that Regulates Both Pathways of Complement Activation and Binds Heparan Sulfate Proteoglycans , 2001, Cell.

[19]  A. Vagin,et al.  MOLREP: an Automated Program for Molecular Replacement , 1997 .

[20]  D. Hourcade,et al.  Decay-accelerating Factor (DAF), Complement Receptor 1 (CR1), and Factor H Dissociate the Complement AP C3 Convertase (C3bBb) via Sites on the Type A Domain of Bb* , 2002, The Journal of Biological Chemistry.

[21]  R. Dwek,et al.  A statistical analysis of N- and O-glycan linkage conformations from crystallographic data. , 1999, Glycobiology.

[22]  T. Gerken,et al.  Role of glycosylation on the conformation and chain dimensions of O-linked glycoproteins: light-scattering studies of ovine submaxillary mucin. , 1989, Biochemistry.

[23]  M. Sternberg,et al.  Rapid refinement of protein interfaces incorporating solvation: application to the docking problem. , 1998, Journal of molecular biology.

[24]  K. Sharp,et al.  Protein folding and association: Insights from the interfacial and thermodynamic properties of hydrocarbons , 1991, Proteins.

[25]  Brian W. Matthews,et al.  An efficient general-purpose least-squares refinement program for macromolecular structures , 1987 .

[26]  J. Platt,et al.  Transgenic pigs expressing human CD59 and decay-accelerating factor produce an intrinsic barrier to complement-mediated damage. , 1997, Transplantation.

[27]  D. Hourcade,et al.  Characterization of the Active Sites in Decay-Accelerating Factor1 , 2001, The Journal of Immunology.

[28]  D. Hourcade,et al.  Decay acceleration of the complement alternative pathway C3 convertase. , 1999, Immunopharmacology.

[29]  O. Spiller,et al.  Mapping CD55 Function , 2003, The Journal of Biological Chemistry.

[30]  R. Dwek,et al.  Analytical and preparative separation of anionic oligosaccharides by weak anion-exchange high-performance liquid chromatography on an inert polymer column. , 1994, Analytical biochemistry.

[31]  J. Volanakis.  The human complement system. , 1975, Journal of oral pathology.

[32]  R. J. Goldberg.  Sedimentation in the Ultracentrifuge , 1953 .

[33]  I. Campbell,et al.  Three-dimensional structure of a complement control protein module in solution. , 1991, Journal of molecular biology.

[34]  H. Fuchs,et al.  Human recombinant soluble decay accelerating factor inhibits complement activation in vitro and in vivo. , 1992, Journal of immunology.

[35]  R. Dwek,et al.  O-Glycan Sialylation and the Structure of the Stalk-like Region of the T Cell Co-receptor CD8* , 2003, Journal of Biological Chemistry.

[36]  P. Evans,et al.  A Structural Explanation for the Binding of Multiple Ligands by the α-Adaptin Appendage Domain , 1999, Cell.

[37]  M. Pangburn,et al.  Differences between the binding sites of the complement regulatory proteins DAF, CR1, and factor H on C3 convertases. , 1986, Journal of immunology.

[38]  Collaborative Computational,et al.  The CCP4 suite: programs for protein crystallography. , 1994, Acta crystallographica. Section D, Biological crystallography.

[39]  R. Smith,et al.  Targeting anticomplement agents. , 2002, Biochemical Society transactions.

[40]  M. Rudolph,et al.  Incorporation of decay-accelerating factor into the baculovirus envelope generates complement-resistant gene transfer vectors , 2001, Nature Biotechnology.

[41]  R. Dwek,et al.  A rapid high-resolution high-performance liquid chromatographic method for separating glycan mixtures and analyzing oligosaccharide profiles. , 1996, Analytical biochemistry.

[42]  Z. Otwinowski,et al.  [20] Processing of X-ray diffraction data collected in oscillation mode. , 1997, Methods in enzymology.

[43]  Jonathan Boyd,et al.  The hairpin structure of the 6F11F22F2 fragment from human fibronectin enhances gelatin binding , 2001, The EMBO journal.

[44]  M. Pangburn,et al.  Biosynthesis and glycosylation of the human complement regulatory protein decay-accelerating factor. , 1986, Journal of immunology.

[45]  G Bricogne,et al.  Direct phase determination by entropy maximization and likelihood ranking: status report and perspectives. , 1993, Acta crystallographica. Section D, Biological crystallography.

[46]  A. Imberty,et al.  Stereochemistry of the N-glycosylation sites in glycoproteins. , 1995, Protein engineering.

[47]  G. Bricogne,et al.  [27] Maximum-likelihood heavy-atom parameter refinement for multiple isomorphous replacement and multiwavelength anomalous diffraction methods. , 1997, Methods in enzymology.

[48]  R. Dwek,et al.  Identification of Specific Glycoforms of Major Histocompatibility Complex Class I Heavy Chains Suggests That Class I Peptide Loading Is an Adaptation of the Quality Control Pathway Involving Calreticulin and ERp57* , 2002, The Journal of Biological Chemistry.

[49]  J. Atkinson,et al.  Decay-Accelerating Factor: Biochemistry, Molecular Biology, and Function , 1989 .

[50]  R. Read.  Improved Fourier Coefficients for Maps Using Phases from Partial Structures with Errors , 1986 .

[51]  R. Dwek,et al.  Glycoproteins: glycan presentation and protein-fold stability. , 1999, Structure.

[52]  C. Mold,et al.  Structure/function studies of human decay‐accelerating factor , 2000, Immunology.

[53]  R. Parekh,et al.  Nonselective and efficient fluorescent labeling of glycans using 2-amino benzamide and anthranilic acid. , 1995, Analytical biochemistry.