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218 a.a.
_CA
Key reference
DOI no: 10.1038/sj.emboj.7601500 EMBO J 26:623-633 (2007) PubMed id: 17215869
Structural insights into the innate immune recognition specificities of L- and H-ficolins. V.Garlatti, N.Belloy, L.Martin, M.Lacroix, M.Matsushita, Y.Endo, T.Fujita, J.C.Fontecilla-Camps, G.J.Arlaud, N.M.Thielens, C.Gaboriaud. ABSTRACT
Innate immunity relies critically upon the ability of a few pattern recognition molecules to sense molecular markers on pathogens, but little is known about these interactions at the atomic level. Human L- and H-ficolins are soluble oligomeric defence proteins with lectin-like activity, assembled from collagen fibers prolonged by fibrinogen-like recognition domains. The X-ray structures of their trimeric recognition domains, alone and in complex with various ligands, have been solved to resolutions up to 1.95 and 1.7 A, respectively. Both domains have three-lobed structures with clefts separating the distal parts of the protomers. Ca(2+) ions are found at sites homologous to those described for tachylectin 5A (TL5A), an invertebrate lectin. Outer binding sites (S1) homologous to the GlcNAc-binding pocket of TL5A are present in the ficolins but show different structures and specificities. In L-ficolin, three additional binding sites (S2-S4) surround the cleft. Together, they define an unpredicted continuous recognition surface able to sense various acetylated and neutral carbohydrate markers in the context of extended polysaccharides such as 1,3-beta-D-glucan, as found on microbial or apoptotic surfaces.
Selected figure(s)
Figure 1.
Figure 1 Homotrimeric structure of the recognition domains of human L- and H-ficolins and location of their binding site(s). (A, B) L-ficolin structure seen from the target binding surface (bottom view) and on a perpendicular side view. (C, D) Corresponding bottom and side views of the H-ficolin structure. The side chains of the binding site residues are displayed as ball and sticks and colored green (S1), red (S2), black (S3), and orange (S4). To enhance clarity of the side view, only one of each representative binding sites is shown on the L-ficolin trimer. N and C indicate the N- and C-terminal ends of each protomer. Ca^2+ ions are represented as golden spheres. Figure generated using MOLSCRIPT (Kraulis, 1991).Figure 3.
Figure 3 Comparative views of the S1 binding site in H-ficolin, L-ficolin, and TL5A. The side chains of the residues defining S1 are colored green and the ligands are displayed in yellow. (A) D-Fucose bound to H-ficolin. (B) GlcNAc bound to TL5A. (C) The terminal mannose of the oligosaccharide chain from a neighboring molecule positioned in site S1 of L-ficolin. On the left, the two proximal GlcNAc residues of the chain interacting on the edge of the binding site.The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: EMBO J (2007, 26, 623-633) copyright 2007. Figures were selected by the author.
Literature references that cite this PDB file's key reference
PubMed id Reference
19129195 I.Söderhäll, C.Wu, M.Novotny, B.L.Lee, and K.Söderhäll (2009).
A Novel Protein Acts as a Negative Regulator of Prophenoloxidase Activation and Melanization in the Freshwater Crayfish Pacifastacus leniusculus.J Biol Chem, 284, 6301-6310.
19180241 J.Zhang, J.Koh, J.Lu, S.Thiel, B.S.Leong, S.Sethi, C.Y.He, B.Ho, and J.L.Ding (2009).
Local inflammation induces complement crosstalk which amplifies the antimicrobial response.PLoS Pathog, 5, e1000282.
18421149 M.Tanio, S.Kondo, S.Sugio, and T.Kohno (2008).
Trimeric structure and conformational equilibrium of M-ficolin fibrinogen-like domain.J Synchrotron Radiat, 15, 243-245.
17938215 Y.Aoyagi, E.E.Adderson, C.E.Rubens, J.F.Bohnsack, J.G.Min, M.Matsushita, T.Fujita, Y.Okuwaki, and S.Takahashi (2008).
L-ficolin/mannose-binding lectin-associated serine protease complexes bind to group B streptococci primarily through N-acetylneuraminic acid of capsular polysaccharide and activate the complement pathway.Infect Immun, 76, 179-188.
17469142 C.Honoré, T.Hummelshoj, B.E.Hansen, H.O.Madsen, P.Eggleton, and P.Garred (2007).
The innate immune component ficolin 3 (Hakata antigen) mediates the clearance of late apoptotic cells.Arthritis Rheum, 56, 1598-1607. 17579066 U.V.Girija, A.W.Dodds, S.Roscher, K.B.Reid, and R.Wallis (2007).
Localization and characterization of the mannose-binding lectin (MBL)-associated-serine protease-2 binding site in rat ficolin-A: equivalent binding sites within the collagenous domains of MBLs and ficolins.J Immunol, 179, 455-462. The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time.
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