Trivalent recognition unit of innate immunity system: crystal structure of trimeric human M-ficolin fibrinogen-like domain.
Ficolins are a kind of pathogen-recognition molecule in the innate immune systems. To investigate the discrimination mechanism between self and non-self by ficolins, we determined the crystal structure of the human M-ficolin fibrinogen-like domain (FD1), which is the ligand-binding domain, at 1.9A resolution. Although the FD1 monomer shares a common fold with the fibrinogen gamma fragment and tachylectin-5A, the Asp-282-Cys-283 peptide bond, which is the predicted ligand-binding site on the C-terminal P domain, is a normal trans bond, unlike the cases of the other two proteins. The trimeric formation of FD1 results in the separation of the three P domains, and the spatial arrangement of the three predicted ligand-binding sites on the trimer is very similar to that of the trimeric collectin, indicating that such an arrangement is generally required for pathogen-recognition. The ligand binding study of FD1 in solution indicated that the recombinant protein binds to N-acetyl-d-glucosamine and the peptide Gly-Pro-Arg-Pro and suggested that the ligand-binding region exhibits a conformational equilibrium involving cis-trans isomerization of the Asp-282-Cys-283 peptide bond. The crystal structure and the ligand binding study of FD1 provide an insight of the self- and non-self discrimination mechanism by ficolins.
Tanio
Michikazu
M
Mitsubishi Kagaku Institute of Life Sciences, 11 Minamiooya, Machida, Tokyo 194-8511, Japan.
Kondo
Shin
S
Sugio
Shigetoshi
S
Kohno
Toshiyuki
T
D001665:Binding Sites; D003094:Collagen / Q000737:chemistry / Q000378:metabolism; D018360:Crystallography, X-Ray; D005340:Fibrinogen / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D007113:Immunity, Innate; D037102:Lectins / Q000737:chemistry* / Q000378:metabolism*; D008024:Ligands; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D000097604:Ficolins
D003094:Collagen; D005340:Fibrinogen; D037102:Lectins; D008024:Ligands; D011994:Recombinant Proteins; D000097604:Ficolins