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PDBsum entry 2wnp
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Immune system
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PDB id
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2wnp
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References listed in PDB file
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Key reference
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Title
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Carbohydrate recognition properties of human ficolins: glycan array screening reveals the sialic acid binding specificity of m-Ficolin.
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Authors
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E.Gout,
V.Garlatti,
D.F.Smith,
M.Lacroix,
C.Dumestre-Pérard,
T.Lunardi,
L.Martin,
J.Y.Cesbron,
G.J.Arlaud,
C.Gaboriaud,
N.M.Thielens.
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Ref.
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J Biol Chem, 2010,
285,
6612-6622.
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PubMed id
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Abstract
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Ficolins are oligomeric innate immune recognition proteins consisting of a
collagen-like region and a fibrinogen-like recognition domain that bind to
pathogen- and apoptotic cell-associated molecular patterns. To investigate their
carbohydrate binding specificities, serum-derived L-ficolin and recombinant H-
and M-ficolins were fluorescently labeled, and their carbohydrate binding
ability was analyzed by glycan array screening. L-ficolin preferentially
recognized disulfated N-acetyllactosamine and tri- and tetrasaccharides
containing terminal galactose or N-acetylglucosamine. Binding was sensitive to
the position and orientation of the bond between N-acetyllactosamine and the
adjacent carbohydrate. No significant binding of H-ficolin to any of the 377
glycans probed could be detected, providing further evidence for its poor lectin
activity. M-ficolin bound preferentially to 9-O-acetylated 2-6-linked sialic
acid derivatives and to various glycans containing sialic acid engaged in a 2-3
linkage. To further investigate the structural basis of sialic acid recognition
by M-ficolin, point mutants were produced in which three residues of the
fibrinogen domain were replaced by their counterparts in L-ficolin. Mutations
G221F and A256V inhibited binding to the 9-O-acetylated sialic acid derivatives,
whereas Y271F abolished interaction with all sialic acid-containing glycans. The
crystal structure of the Y271F mutant fibrinogen domain was solved, showing that
the mutation does not alter the structure of the ligand binding pocket. These
analyses reveal novel ficolin ligands such as sulfated N-acetyllactosamine
(L-ficolin) and gangliosides (M-ficolin) and provide precise insights into the
sialic acid binding specificity of M-ficolin, emphasizing the essential role of
Tyr(271) in this respect.
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