Factor D C 3 b B Factor B
Factor D C 3 b. B Factor B C 3 b Ba C 3 b. Bb C 4 b 2 a C 4 a + C 2 b C 3 activated C 1 s C 3 b. Bb 3 b C 5 C 4 b 2 a 3 b C 5 a C 5 b C 9 C 8 C 7 C 6 C 5 b 6789 Terminal complex Figure 1. 1. Schematic overview of the complement system. The three activation pathways all merge in the formation of a C 3 convertase complex. After formation of the C 3 convertase the C 5 convertase complex can be generated enabling the formation of the terminal complex (or membrane attack complex) which can be formed on exposed plasma membranes. The cleavage products in red all have anaphylotoxin effects of which C 5 a is the most potent. C 3(H 2 O)Bb C 3 Alternative pathway MBL/Ficolins + MASP-1 MASP-2 MASP-3 Lectin pathway C 2 + C 4 C 1 q + C 1 r + C 1 s Classical pathway
Figure 1. 2. The mechanism by which C 4 b or C 3 b is bound covalently to a surface. Upon activation/cleavage of C 4 structural rearrangements occur whereby the thiolester bond in C 4 b becomes exposed and reacts with active groups on nearby surfaces (R). This results in formation of an ester or amide bond between C 4 b or C 3 b and the surface. The figure was adapted from Law and Dodds (1997).
Figure 1. 3. The polypeptide structure of C 3 and its activation and degradation products. The position of the internal thiolester bond is indicated by a triangle, which upon conversion of C 3 into C 3 b is broken and indicated by two parallel lines. The figure is modified from Law and Dodds, (1997).
A B Figure 1. 4. A schematic representation of the C 1 complex. Panel A shows C 1 from the side while panel B shows it from below. The catalytic domain of C 1 r. A is purple and of C 1 r. B brown, while the CUB 2 modules of the two C 1 r molecules are colored gray. For clarity the CUB and the catalytic domains of C 1 s have been omitted. This figure is adapted from Gregory et al. , (2003).
Polypeptide chain x 3 Trimeric subunit x 6 Hexameric oligomer Figure 1. 5. The assembly of the hexameric MBL oligomer. Three MBL polypeptide chains associate generating the trimeric subunit. The MBL subunits can further associate to complexes composed of 2 -6 trimeric subunits (here only the hexamer is shown). This figure is adapted from Presanis et al. , (2003).
Figure 1. 6. Exon organization of the human ficolin genes. The boxes depict the exon structure of the ficolins and the corresponding protein domains are indicated by the ficolin subunit below for L-ficolin (L-FCN), M-ficolin (MFCN) and H-ficolin (H-FCN). Modified from Endo et al. , (2007).
Figure 1. 7. The subunit structure of MBL and the ficolins, drawn approximately to scale regarding the length of the collagen-like domain. The break in the collagen-like domain indicates the position of the disruption in the Gly-Xaa-Yaa triplets. The figure is modified from Holmskov et al. , (2003).
A B H-ficolin M-ficolin L-ficolin 53 83 M-ficolin 52 Figure 1. 8. Similarity between L-ficolin, M-ficolin and H-ficolin. Panel A shows an alignment of L-ficolin (SWISS-Prot entry: Q 15485), M-ficolin (SWISS-Prot entry: O 00602) and H-ficolin (Swiss-Prot entry: O 75636) primary sequence. The alignment was performed with the Clustal. W program (http: //www. ebi. ac. uk/Tools/clustalw/index. html). The asterisks (*) represent exact matches, (: ) represent conservative substitutions and (. ) represent semi-conservative substitutions. The sequence in red is considered a part of the fbg domain. Panel B shows the pair-wise identity of the three ficolins in the fbg domain.
Figure 1. 9. Schematic diagram of the L-ficolin trimeric subunit and the L-ficolin tetramer. This figure is modified from Ohashi and Erickson, (1998)
A B Figure 1. 10. Structure of the L-ficolin fbg domain. Panel A shows the crystal structure of the L-ficolin trimeric subunit (seen from below). The amino acid side chains involved in the recognition of the ligands in the four recognition sites are coloured as follows: S 1 (green), S 2 (red), S 3 (black) and S 4 (orange). A Ca 2+ ion (yellow) is also found in the domain, but it is not directly involved in the ligand recognition. Panel B shows the proposed collaboration between sites S 2 -4 in mediating binding to oligosaccharides. This figure is adapted from Garlatti et al. , (2007 a).
Figure 1. 11. The structure of the fbg domain of M-ficolin. The structure of the Mficolin trimer with a Glc. NAc molecule (green) at the predicted binding site seen from below (top) and the side (bottom). The 50 Å a rough indication of the dimensions of the molecule. This figure is adapted from Tanio et al. , (2006).
Figure 1. 12. The structure of the H-ficolin fbg domain. The amino acid side chains involved in the ligand recognition are shown in green. The yellow sphere is a Ca 2+ ion. This figure is adapted from Garlatti et al. , (2007 a).
1 2 3 4 5 4 6 5 6 7 7 8 9 8 10 9 10 12 13 11 11 14 15 16 17 12 Figure 1. 13. Genomic organization and protein structure of the MASP 1/3 and MASP 2/MAp 19 genes. Shown is the intron-exon structure of the two genes and their protein products. The arrow indicates the Arg-Ile bond that is cleaved upon MASP activation. The asterisks denotes potential N-linked glycosylation sites. The figure is modified from Schwaeble et al. , (2002)
Figure 1. 14. The homodimeric structure of MAp 19. Top view (top) and side view (bottom) of the homodimeric MAp 19 complex. The amino acid side chains involved in the interactions between the two MAp 19 molecules are indicated. The Ca 2+ ions are represented as golden spheres. This figure is adapted from Gregory et al. , (2004).
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