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Article

  • The EMBO Journal (2007) 26, 623 - 633
  • doi:10.1038/sj.emboj.7601500

Published online: 11 January 2007

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

Virginie Garlatti1, Nicolas Belloy1, Lydie Martin1, Monique Lacroix2, Misao Matsushita3, Yuichi Endo4, Teizo Fujita4, Juan Carlos Fontecilla-Camps1, Gérard J Arlaud2, Nicole M Thielens2 and Christine Gaboriaud1

  1. Laboratoire de Cristallographie et Cristallogénèse des Protéines, Grenoble, France
  2. Laboratoire d'Enzymologie Moléculaire, Institut de Biologie Structurale Jean-Pierre Ebel, CEA; CNRS; Université Joseph Fourier, Grenoble, France
  3. Department of Applied Biochemistry, Institute of Glycotechnology, Tokai University, Hiratsuka, Kanagawa, Japan
  4. Department of Biochemistry, Fukushima Medical University School of Medicine, Fukushima, Japan

Correspondence to:

Christine Gaboriaud, Laboratoire de Cristallographie et Cristallogénèse des Protéines, Institut de Biologie Structurale Jean-Pierre Ebel, 41, rue Jules Horowitz, Grenoble cedex 1, 38041, France. Tel.: +33 4 38 78 95 99; Fax: +33 4 38 78 51 22; E-mail: christine.gaboriaud@ibs.fr

Received 2 August 2006; Accepted 31 October 2006

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-beta-D-glucan, as found on microbial or apoptotic surfaces.

  • Keywords:

    • carbohydrate recognition,
    • fibrinogen-like domain,
    • innate immunity,
    • N-acetyl group,
    • X-ray crystallography