Structural insights into the innate immune recognition specificities of L- and H-ficolins

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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 Å, respectively. Both domains have three‐lobed structures with clefts separating the distal parts of the protomers. Ca2+ 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‐β‐d‐glucan, as found on microbial or apoptotic surfaces.