3AP6

Crystal structure of the galectin-8 N-terminal carbohydrate recognition domain in complex with lactose 3'-sulfate

Summary for 3AP6

• Entry DOI: 10.2210/pdb3ap6/pdb
• Related: 3AP4 3AP5 3AP7
• Related PRD ID: PRD_900004
• Descriptor: Galectin-8, beta-D-galactopyranose-(1-4)-beta-D-glucopyranose, SULFATE ION, ... (4 entities in total)
• Functional Keywords: beta-sandwich, galectin, carbohydrate/sugar binding, sugar binding protein
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm (Probable): O00214
• Total number of polymer chains: 4
• Total formula weight: 71445.93

Authors

Matsuzaka, T.,Ideo, H.,Yamashita, K.,Nonaka, T. (deposition date: 2010-10-12, release date: 2011-01-26, Last modification date: 2023-11-01)

Primary citation

Ideo, H.,Matsuzaka, T.,Nonaka, T.,Seko, A.,Yamashita, K.
Galectin-8-N-domain recognition mechanism for sialylated and sulfated glycans
J.Biol.Chem., 286:11346-11355, 2011

PubMed 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, Arg(45), Gln(47), Arg(59), 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 Tyr(141), 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 Arg(45), Gln(47), and Arg(59) of galectin-8N are indispensable and coordinately contribute to the strong binding of galectins-8N to sialylated and sulfated oligosaccharides. Arg(59) is the most critical amino acid for binding in the S3-S4 loop region.

PubMed: 21288902
DOI: 10.1074/jbc.M110.195925

Experimental method

X-RAY DIFFRACTION (1.58 Å)