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Intra- and inter-molecular interactions of human galectin-3: assessment by full-assignment-based NMR.

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Author

  • Hans Ippel
  • Michelle C Miller
  • Sabine Vértesy
  • Yi Zhang
  • F Javier Cañada
  • Dennis Suylen
  • Kimiko Umemoto
  • Cecilia Romanò
  • Tilman Hackeng
  • Guihua Tai
  • Hakon Leffler
  • Jürgen Kopitz
  • Sabine André
  • Dieter Kübler
  • Jesús Jiménez-Barbero
  • Stefan Oscarson
  • Hans-Joachim Gabius
  • Kevin H Mayo
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Summary, in English

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 (13)C/(15)N-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 β-sheet behind the canonical carbohydrate-binding 6-stranded β-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. Lastly, 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 β-galactosides.

Publishing year

2016-02-23

Language

English

Pages

888-903

Publication/Series

Glycobiology

Volume

26

Issue

8

Document type

Journal article

Publisher

Oxford University Press

Topic

  • Structural Biology

Status

Published

ISBN/ISSN/Other

  • ISSN: 1460-2423