Structural Basis Underlying the Binding Preference of Human Galectins-1, -3 and -7 for Galβ1-3/4GlcNAc

PLoS One. 2015 May 6;10(5):e0125946. doi: 10.1371/journal.pone.0125946. eCollection 2015.

Abstract

Galectins represent β-galactoside-binding proteins and are known to bind Galβ1-3/4GlcNAc disaccharides (abbreviated as LN1 and LN2, respectively). Despite high sequence and structural homology shared by the carbohydrate recognition domain (CRD) of all galectin members, how each galectin displays different sugar-binding specificity still remains ambiguous. Herein we provided the first structural evidence of human galectins-1, 3-CRD and 7 in complex with LN1. Galectins-1 and 3 were shown to have higher affinity for LN2 than for LN1, while galectin-7 displayed the reversed specificity. In comparison with the previous LN2-complexed structures, the results indicated that the average glycosidic torsion angle of galectin-bound LN1 (ψ(LN1) ≈ 135°) was significantly differed from that of galectin-bound LN2 (ψ(LN2 )≈ -108°), i.e. the GlcNAc moiety adopted a different orientation to maintain essential interactions. Furthermore, we also identified an Arg-Asp/Glu-Glu-Arg salt-bridge network and the corresponding loop (to position the second Asp/Glu residue) critical for the LN1/2-binding preference.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Proteins
  • Crystallography, X-Ray
  • Disaccharides / chemistry
  • Disaccharides / metabolism*
  • Galactosides / chemistry
  • Galactosides / metabolism*
  • Galectin 1 / metabolism*
  • Galectin 3 / metabolism*
  • Galectins / metabolism*
  • Humans
  • Protein Binding

Substances

  • Blood Proteins
  • Disaccharides
  • Galactosides
  • Galectin 1
  • Galectin 3
  • Galectins
  • LGALS1 protein, human
  • LGALS3 protein, human
  • LGALS7 protein, human
  • beta-galactoside

Associated data

  • PDB/4XBL
  • PDB/4XBN
  • PDB/4XBQ

Grants and funding

This work was supported by Academia Sinica, and Ministry of Science and Technology grants: AS-022316 (to C.-H. Lin), NSC-103-2113-M-001-023-MY3 (to C.-H. Lin), NSC-102-2113-M-001-001-MY3 (to C.-H. Lin), and NSC-102-2923-M-001-001-MY3 (to C.-H. Lin). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.