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

FEBS J. 2012 Oct;279(20):3937-51. doi: 10.1111/j.1742-4658.2012.08753.x. Epub 2012 Sep 11.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Binding Sites / genetics
  • Carbohydrate Sequence
  • Carbohydrates / chemistry
  • Crystallography, X-Ray
  • Galectins / chemistry*
  • Galectins / genetics
  • Galectins / metabolism
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Molecular Structure
  • Mutant Proteins / chemistry*
  • Mutant Proteins / genetics
  • Mutant Proteins / metabolism
  • Mutation
  • Oligosaccharides / chemistry*
  • Oligosaccharides / metabolism
  • Peptide Hydrolases / metabolism
  • Protein Binding
  • Protein Multimerization
  • Protein Structure, Tertiary*
  • Sequence Homology, Amino Acid
  • Sialic Acids / chemistry
  • Sialic Acids / metabolism
  • Substrate Specificity

Substances

  • Carbohydrates
  • Galectins
  • LGALS8 protein, human
  • Mutant Proteins
  • Oligosaccharides
  • Sialic Acids
  • Peptide Hydrolases

Associated data

  • PDB/3VKL
  • PDB/3VKM
  • PDB/3VKN
  • PDB/3VKO
  • PDB/4FQZ