X-ray Structures of Human Galectin-9 C-terminal Domain in Complexes with a Biantennary Oligosaccharide and Sialyllactose

Yoshida, Hiromi; Teraoka, Misa; Nishi, Nozomu; Nakakita, Shin‐ichi; Nakamura, Takanori; Hirashima, Mitsuomi; Kamitori, Shigehiro

doi:10.1074/jbc.m110.163402

Cited by 43 publications

(29 citation statements)

References 42 publications

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“…Structural comparison of N‐CRDs and C‐CRDs could explain the difference in specificity. Arg59, located in the long S3–S4 loop particular to G8N, is responsible for the strong affinity for α2–3‐sialylated oligosaccharides, and Arg45 and Gln47 also help to recognize a sialic acid moiety, as previously proposed by us on the basis of the G9C structure and as recently reported by Ideo et al . on the basis of the G8N structure .…”

Section: Discussionsupporting

confidence: 75%

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X‐ray structure of a protease‐resistant mutant form of human galectin‐8 with two carbohydrate recognition domains

et al. 2012

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Galectin-8 is a tandem-repeat-type b-galactoside-specific animal lectin possessing N-terminal and C-terminal carbohydrate recognition domains (N-CRD and C-CRD, respectively), with a difference in carbohydratebinding specificity, involved in cell-matrix interaction, malignant transformation, and cell adhesion. N-CRD shows strong affinity for a2-3-sialylated oligosaccharides, a feature unique to galectin-8. C-CRD usually shows lower affinity for oligosaccharides but higher affinity for N-glycan-type branched oligosaccharides than does N-CRD. There have been many structural studies on galectins with a single carbohydrate recognition domain (CRD), but no X-ray structure of a galectin containing both CRDs has been reported. Here, the X-ray structure of a protease-resistant mutant form of human galectin-8 possessing both CRDs and the novel pseudodimer structure of galectin-8 N-CRD in complexes with a2-3-sialylated oligosaccharide ligands were determined. The results revealed a difference in specificity between N-CRD and C-CRD, and provided new insights into the association of CRDs and/or molecules of galectin-8. DatabaseThe atomic coordinates and structure factors of G8Null-Lac, G8Null-2Lac, G8Null-SiaLacLac, G8N-free and G8N-SiaLacNAc have been deposited in the Protein Data Bank under the accession codes 4FQZ, 3VKL, 3VKM, 3VKN, and 3VKO, respectively. Structured digital abstractG8 and G8 bind by x-ray crystallography (View interaction)

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Section: Discussionsupporting

confidence: 75%

“…Structural studies on galectins alone and in complexes with oligosaccharides have provided important clues about their structure–function relationships . Recently, Ideo et al .…”

Section: Introductionmentioning

confidence: 99%

X‐ray structure of a protease‐resistant mutant form of human galectin‐8 with two carbohydrate recognition domains

et al. 2012

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“…In case of lactose and LacNAc, O3 is hydrogen bonded to E76, whereas for lacto-N-biose it is O4. The N-acetyl group of LacNAc interacts with E78 in a similar way as found for human galectin-9C [28]. The complexes of Gal-8 C-CRD with LacNAc and lactose are shown in Figure 3A and 3C , respectively.…”

Section: Resultssupporting

confidence: 57%

“…The amino acid numbering of Gal-8C (PDB ID: 3OJB) has been used in this study. For sequence alignments and structural superimposition with Gal-8C domain, Gal-1 (PDB ID: 1GZW) [37], Gal-2 (PDB ID: 1HLC) [38], Gal-3 (PDB ID: 1A3K) [32], Gal-4C (1X50), Gal-9N (PDB ID: 2ZHM) [35] and Gal-9C (3NV1) [28] were also retrieved.…”

Section: Methodsmentioning

confidence: 99%

Understanding the Specificity of Human Galectin-8C Domain Interactions with Its Glycan Ligands Based on Molecular Dynamics Simulations

2013

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Human Galectin-8 (Gal-8) is a member of the galectin family which shares an affinity for β-galactosides. The tandem-repeat Gal-8 consists of a N- and a C-terminal carbohydrate recognition domain (N- and C-CRD) joined by a linker peptide of various length. Despite their structural similarity both CRDs recognize different oligosaccharides. While the molecular requirements of the N-CRD for high binding affinity to sulfated and sialylated glycans have recently been elucidated by crystallographic studies of complexes with several oligosaccharides, the binding specificities of the C-CRD for a different set of oligosaccharides, as derived from experimental data, has only been explained in terms of the three-dimensional structure for the complex C-CRD with lactose. In this study we performed molecular dynamics (MD) simulations using the recently released crystal structure of the Gal-8C-CRD to analyse the three-dimensional conditions for its specific binding to a variety of oligosaccharides as previously defined by glycan-microarray analysis. The terminal β-galactose of disaccharides (LacNAc, lacto-N-biose and lactose) and the internal β-galactose moiety of blood group antigens A and B (BGA, BGB) as well as of longer linear oligosaccharide chains (di-LacNAc and lacto-N-neotetraose) are interacting favorably with conserved amino acids (H53, R57, N66, W73, E76). Lacto-N-neotetraose and di-LacNAc as well as BGA and BGB are well accommodated BGA and BGB showed higher affinity than LacNAc and lactose due to generally stronger hydrogen bond interactions and water mediated hydrogen bonds with α1-2 fucose respectively. Our results derived from molecular dynamics simulations are able to explain the glycan binding specificities of the Gal-8C-CRD in comparison to those of the Gal-8N -CRD.

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“…5). In a recent study, the structure of the full-length mutant galectin-8 was determined, and the linker domain of mutant galectin-8 was replaced by only two amino acids, signifying that the length of the linker domain in galectins had an effect on the formation of crystals (24). Conversely, the short linker domain of Tl-gal was influenced by the structural stability.…”

Section: Discussionmentioning

confidence: 99%

Structural Basis for Carbohydrate Recognition and Anti-inflammatory Modulation by Gastrointestinal Nematode Parasite Toxascaris leonina Galectin

Hwang

Jeong

Park

et al. 2016

Journal of Biological Chemistry

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Edited by Luke O'NeillToxascaris leonina galectin (Tl-gal) is a galectin-9 homologue protein isolated from an adult worm of the canine gastrointestinal nematode parasite, and Tl-gal-vaccinated challenge can inhibit inflammation in inflammatory bowel disease-induced mice. We determined the first X-ray structures of full-length Tl-gal complexes with carbohydrates (lactose, N-acetyllactosamine, lacto-N-tetraose, sialyllactose, and glucose). Bonds were formed on concave surfaces of both carbohydrate recognition domains (CRDs) in Tl-gal. All binding sites were found in the HXXXR and WGXEER motifs. Charged Arg 61 /Arg 196 and Glu 80 /Glu 215 on the conserved motif of Tl-gal N-terminal CRD and C-terminal CRD are critical amino acids for recognizing carbohydrate binding, and the residues can affect protein folding and structure. The polar amino acids His, Asn, and Trp are also important residues for the interaction with carbohydrates through hydrogen bonding. Hemagglutination activities of Tlgal were inhibited by interactions with carbohydrates and mutations. We found that the mutation of Tl-gal (E80A/E215A) at the carbohydrate binding region induced protein aggregation and could be caused in many diseases. The short linker region between the N-terminal and C-terminal CRDs of Tl-gal was very stable against proteolysis and maintained its biological activity. This structural information is expected to elucidate the carbohydrate recognition mechanism of Tl-gal and improve our understanding of anti-inflammatory mediators and modulators of immune response.

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X-ray Structures of Human Galectin-9 C-terminal Domain in Complexes with a Biantennary Oligosaccharide and Sialyllactose

Cited by 43 publications

References 42 publications

X‐ray structure of a protease‐resistant mutant form of human galectin‐8 with two carbohydrate recognition domains

X‐ray structure of a protease‐resistant mutant form of human galectin‐8 with two carbohydrate recognition domains

Understanding the Specificity of Human Galectin-8C Domain Interactions with Its Glycan Ligands Based on Molecular Dynamics Simulations

Structural Basis for Carbohydrate Recognition and Anti-inflammatory Modulation by Gastrointestinal Nematode Parasite Toxascaris leonina Galectin

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