3aya Citations

Structural basis for distinct binding properties of the human galectins to Thomsen-Friedenreich antigen.

OpenAccess logo PLoS One 6 e25007 (2011)
Related entries: 3ayc, 3ayd, 3aye

Cited: 46 times
EuropePMC logo PMID: 21949831

Abstract

The Thomsen-Friedenreich (TF or T) antigen, Galβ1-3GalNAcα1-O-Ser/Thr, is the core 1 structure of O-linked mucin type glycans appearing in tumor-associated glycosylation. The TF antigen occurs in about 90% of human cancer cells and is a potential ligand for the human endogenous galectins. It has been reported that human galectin-1 (Gal-1) and galectin-3 (Gal-3) can perform their cancer-related functions via specifically recognizing TF antigen. However, the detailed binding properties have not been clarified and structurally characterized. In this work, first we identified the distinct TF-binding abilities of Gal-1 and Gal-3. The affinity to TF antigen for Gal-3 is two orders of magnitude higher than that for Gal-1. The structures of Gal-3 carbohydrate recognition domain (CRD) complexed with TF antigen and derivatives, TFN and GM1, were then determined. These structures show a unique Glu-water-Arg-water motif-based mode as previously observed in the mushroom galectin AAL. The observation demonstrates that this recognition mode is commonly adopted by TF-binding galectins, either as endogenous or exogenous ones. The detailed structural comparisons between Gal-1 and Gal-3 CRD and mutagenesis experiments reveal that a pentad residue motif ((51)AHGDA(55)) at the loop (g1-L4) connecting β-strands 4 and 5 of Gal-1 produces a serious steric hindrance for TF binding. This motif is the main structural basis for Gal-1 with the low affinity to TF antigen. These findings provide the intrinsic structural elements for regulating the TF-binding activity of Gal-1 in some special conditions and also show certain target and approach for mediating some tumor-related bioactivities of human galectins.

Reviews - 3aya mentioned but not cited (1)

Articles - 3aya mentioned but not cited (2)

  1. Structural basis for distinct binding properties of the human galectins to Thomsen-Friedenreich antigen. Bian CF, Zhang Y, Sun H, Li DF, Wang DC. PLoS One 6 e25007 (2011)
  2. Thermodynamic Switch in Binding of Adhesion/Growth Regulatory Human Galectin-3 to Tumor-Associated TF Antigen (CD176) and MUC1 Glycopeptides. Rodriguez MC, Yegorova S, Pitteloud JP, Chavaroche AE, André S, Ardá A, Minond D, Jiménez-Barbero J, Gabius HJ, Cudic M. Biochemistry 54 4462-4474 (2015)


Reviews citing this publication (11)

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  3. Galectin-3 as a Potential Target to Prevent Cancer Metastasis. Ahmed H, AlSadek DM. Clin Med Insights Oncol 9 113-121 (2015)
  4. Targeting Galectins With Glycomimetics. Bertuzzi S, Quintana JI, Ardá A, Gimeno A, Jiménez-Barbero J. Front Chem 8 593 (2020)
  5. Synthetic glycoconjugates inhibitors of tumor-related galectin-3: an update. Campo VL, Marchiori MF, Rodrigues LC, Dias-Baruffi M. Glycoconj J 33 853-876 (2016)
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