Structural insights into the innate immune recognition specificities of L- and H-ficolins.
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.
Garlatti
Virginie
V
Laboratoire de Cristallographie et Cristallogénèse des Protéines, Grenoble, France.
Belloy
Nicolas
N
Martin
Lydie
L
Lacroix
Monique
M
Matsushita
Misao
M
Endo
Yuichi
Y
Fujita
Teizo
T
Fontecilla-Camps
Juan Carlos
JC
Arlaud
Gérard J
GJ
Thielens
Nicole M
NM
Gaboriaud
Christine
C
D000107:Acetylation; D000123:Acetyltransferases / Q000378:metabolism; D000595:Amino Acid Sequence; D001665:Binding Sites; D005690:Galactose / Q000378:metabolism; D006023:Glycoproteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D037102:Lectins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity; D047071:beta-Glucans / Q000378:metabolism; D000097604:Ficolins
D000123:Acetyltransferases; D005690:Galactose; D006023:Glycoproteins; D037102:Lectins; D008024:Ligands; D021122:Protein Subunits; D047071:beta-Glucans; D000097604:Ficolins; C109662:FCN3 protein, human; C033363:beta-1,3-glucan