Intra- and intermolecular interactions of human galectin-3: assessment by full-assignment-based NMR

Hans Ippel, Michelle C. Miller, Sabine Vertesy, Yi Zheng, F. Javier Canada, Dennis Suylen, Kimiko Umemoto, Cecilia Romano, Tilman Hackeng, Guihua Tai, Hakon Leffler, Juergen Kopitz, Sabine Andre, Dieter Kuebler, Jesos Jimenez-Barbero, Stefan Oscarson, Hans-Joachim Gabius, K.H. Mayo*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Galectin-3 is an adhesion/growth-regulatory protein with a modular design comprising an N-terminal tail ( NT, residues 1-111) and the conserved carbohydrate recognition domain ( CRD, residues 112-250). The chimera-type galectin interacts with both glycan and peptide motifs. Complete C-13/N-15-assignment of the human protein makes NMR-based analysis of its structure beyond the CRD possible. Using two synthetic NT polypeptides covering residues 1-50 and 51-107, evidence for transient secondary structure was found with helical conformation from residues 5 to 15 as well as proline-mediated, multi-turn structure from residues 18 to 32 and around PGAYP repeats. Intramolecular interactions occur between the CRD F-face ( the 5-stranded beta-sheet behind the canonical carbohydrate-binding 6-stranded beta-sheet of the S-face) and NT in full-length galectin-3, with the sequence P(23)GAW(26)... P(37)GASYPGAY(45) defining the primary binding epitope within the NT. Work with designed peptides indicates that the PGAX motif is crucial for self-interactions between NT/CRD. Phosphorylation at position Ser6 ( and Ser12) ( a physiological modification) and the influence of ligand binding have minimal effect on this interaction. Finally, galectin-3 molecules can interact weakly with each other via the F-faces of their CRDs, an interaction that appears to be assisted by their NTs. Overall, our results add insight to defining binding sites on galectin-3 beyond the canonical contact area for beta-galactosides.
Original languageEnglish
Pages (from-to)888-903
Issue number8
Publication statusPublished - Aug 2016


  • adhesion
  • apoptosis
  • lectin
  • phosphorylation
  • self-association


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