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Galectin-8-N-domain Recognition Mechanism for Sialylated and Sulfated Glycans*

By Hiroko Ideo, Tsutomu Matsuzaka, Takamasa Nonaka, Akira Seko and Katsuko Yamashita

Abstract

Galectin-8 has much higher affinity for 3′-O-sulfated or 3′-O-sialylated glycoconjugates and a Lewis X-containing glycan than for oligosaccharides terminating in Galβ1→3/4GlcNAc, and this specificity is mainly attributed to the N-terminal carbohydrate recognition domain (N-domain, CRD) (Ideo, H., Seko, A., Ishizuka, I., and Yamashita, K. (2003) Glycobiology 13, 713–723). In this study, we elucidated the crystal structures of the human galectin-8-N-domain (-8N) in the absence or presence of 4 ligands. The apo molecule forms a dimer, which is different from the canonical 2-fold symmetric dimer observed for galectin-1 and -2. In a galectin-8N-lactose complex, the lactose-recognizing amino acids are highly conserved among the galectins. However, Arg45, Gln47, Arg59, and the long loop region between the S3 and S4 β-strands are unique to galectin-8N. These amino acids directly or indirectly interact with the sulfate or sialic acid moieties of 3′-sialyl- and 3′-sulfolactose complexed with galectin-8N. Furthermore, in the LNF-III-galectin-8N complex, van der Waals interactions occur between the α1–3-branched fucose and galactose and between galactose and Tyr141, and these interactions increase the affinity toward galectin-8N. Based on the findings of these x-ray crystallographic analyses, a mutagenesis study using surface plasmon resonance showed that Arg45, Gln47, and Arg59 of galectin-8N are indispensable and coordinately contribute to the strong binding of galectins-8N to sialylated and sulfated oligosaccharides. Arg59 is the most critical amino acid for binding in the S3–S4 loop region

Topics: Glycobiology and Extracellular Matrices
Publisher: American Society for Biochemistry and Molecular Biology
OAI identifier: oai:pubmedcentral.nih.gov:3064191
Provided by: PubMed Central
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