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

Yoshida H, Yamashita S, Teraoka M, Itoh A, Nakakita S, Nishi N, Kamitori S
FEBS J 279 3937-51 (2012)
Related entries: 3vkl, 3vkm, 3vkn, 4fqz

Cited: 24 times
EuropePMC logo PMID: 22913484

Abstract

Galectin-8 is a tandem-repeat-type β-galactoside-specific animal lectin possessing N-terminal and C-terminal carbohydrate recognition domains (N-CRD and C-CRD, respectively), with a difference in carbohydrate-binding specificity, involved in cell-matrix interaction, malignant transformation, and cell adhesion. N-CRD shows strong affinity for α2-3-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 α2-3-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.

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  1. Role of N-glycosylation in activation of proMMP-9. A molecular dynamics simulations study. Kumar S, Cieplak P. PLoS One 13 e0191157 (2018)
  2. Oligosaccharide Presentation Modulates the Molecular Recognition of Glycolipids by Galectins on Membrane Surfaces. Lete MG, Franconetti A, Delgado S, Jiménez-Barbero J, Ardá A. Pharmaceuticals (Basel) 15 145 (2022)


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  1. Galectin-8: a matricellular lectin with key roles in angiogenesis. Troncoso MF, Ferragut F, Bacigalupo ML, Cárdenas Delgado VM, Nugnes LG, Gentilini L, Laderach D, Wolfenstein-Todel C, Compagno D, Rabinovich GA, Elola MT. Glycobiology 24 907-914 (2014)
  2. A Brief History of Charcot-Leyden Crystal Protein/Galectin-10 Research. Su J. Molecules 23 E2931 (2018)
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  5. Sialic acid as a target for the development of novel antiangiogenic strategies. Chiodelli P, Urbinati C, Paiardi G, Monti E, Rusnati M. Future Med Chem 10 2835-2854 (2018)

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  1. Structural basis for recognition of autophagic receptor NDP52 by the sugar receptor galectin-8. Kim BW, Hong SB, Kim JH, Kwon DH, Song HK. Nat Commun 4 1613 (2013)
  2. Natural single amino acid polymorphism (F19Y) in human galectin-8: detection of structural alterations and increased growth-regulatory activity on tumor cells. Ruiz FM, Scholz BA, Buzamet E, Kopitz J, André S, Menéndez M, Romero A, Solís D, Gabius HJ. FEBS J 281 1446-1464 (2014)
  3. Structural characterization of human galectin-4 C-terminal domain: elucidating the molecular basis for recognition of glycosphingolipids, sulfated saccharides and blood group antigens. Bum-Erdene K, Leffler H, Nilsson UJ, Blanchard H. FEBS J 282 3348-3367 (2015)
  4. Teaming up synthetic chemistry and histochemistry for activity screening in galectin-directed inhibitor design. Roy R, Cao Y, Kaltner H, Kottari N, Shiao TC, Belkhadem K, André S, Manning JC, Murphy PV, Gabius HJ. Histochem Cell Biol 147 285-301 (2017)
  5. Structural significance of galectin design: impairment of homodimer stability by linker insertion and partial reversion by ligand presence. Vértesy S, Michalak M, Miller MC, Schnölzer M, André S, Kopitz J, Mayo KH, Gabius HJ. Protein Eng Des Sel 28 199-210 (2015)
  6. Combining Crystallography and Hydrogen-Deuterium Exchange to Study Galectin-Ligand Complexes. Ruiz FM, Gilles U, Lindner I, André S, Romero A, Reusch D, Gabius HJ. Chemistry 21 13558-13568 (2015)
  7. Galectin-8 binds to the Farnesylated C-terminus of K-Ras4B and Modifies Ras/ERK Signaling and Migration in Pancreatic and Lung Carcinoma Cells. Meinohl C, Barnard SJ, Fritz-Wolf K, Unger M, Porr A, Heipel M, Wirth S, Madlung J, Nordheim A, Menke A, Becker K, Giehl K. Cancers (Basel) 12 E30 (2019)
  8. Full-length model of the human galectin-4 and insights into dynamics of inter-domain communication. Rustiguel JK, Soares RO, Meisburger SP, Davis KM, Malzbender KL, Ando N, Dias-Baruffi M, Nonato MC. Sci Rep 6 33633 (2016)
  9. The Impact of Natural Selection on the Evolution and Function of Placentally Expressed Galectins. Ely ZA, Moon JM, Sliwoski GR, Sangha AK, Shen XX, Labella AL, Meiler J, Capra JA, Rokas A. Genome Biol Evol 11 2574-2592 (2019)
  10. Heterologous expression of newly identified galectin-8 from sea urchin embryos produces recombinant protein with lactose binding specificity and anti-adhesive activity. Karakostis K, Costa C, Costa C, Zito F, Matranga V. Sci Rep 5 17665 (2015)
  11. Deep phylogenomics of a tandem-repeat galectin regulating appendicular skeletal pattern formation. Bhat R, Chakraborty M, Glimm T, Stewart TA, Newman SA. BMC Evol Biol 16 162 (2016)
  12. Molecular characterization of Galectin-8 from Nile tilapia (Oreochromis niloticus Linn.) and its response to bacterial infection. Unajak S, Pholmanee N, Songtawee N, Srikulnath K, Srisapoome P, Kiataramkul A, Kondo H, Hirono I, Areechon N. Mol Immunol 68 585-596 (2015)
  13. The two domains of human galectin-8 bind sialyl- and fucose-containing oligosaccharides in an independent manner. A 3D view by using NMR. Gómez-Redondo M, Delgado S, Núñez-Franco R, Jiménez-Osés G, Ardá A, Jiménez-Barbero J, Gimeno A. RSC Chem Biol 2 932-941 (2021)
  14. NMR assignments of the C-terminal domain of human galectin-8. Liu CH, Chien CT, Lin CH, Hsu ST. Biomol NMR Assign 9 427-430 (2015)
  15. Studying the Structural Significance of Galectin Design by Playing a Modular Puzzle: Homodimer Generation from Human Tandem-Repeat-Type (Heterodimeric) Galectin-8 by Domain Shuffling. Ludwig AK, Michalak M, Shilova N, André S, Kaltner H, Bovin NV, Kopitz J, Gabius HJ. Molecules 22 E1572 (2017)
  16. X-ray structure of a protease-resistant mutant form of human galectin-9 having two carbohydrate recognition domains with a metal-binding site. Yoshida H, Nishi N, Wada K, Nakamura T, Hirashima M, Kuwabara N, Kato R, Kamitori S. Biochem Biophys Res Commun 490 1287-1293 (2017)
  17. Discovery of N-Arylsulfonyl-Indole-2-Carboxamide Derivatives as Galectin-3 and Galectin-8 C-Terminal Domain Inhibitors. Zhang H, Wang X, Wan Y, Liu L, Zhou J, Li P, Xu B. ACS Med Chem Lett 14 1257-1265 (2023)


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