Human chimera-type galectin-3: defining the critical tail length for high-affinity glycoprotein/cell surface binding and functional competition with galectin-1 in neuroblastoma cell growth regulation

Biochimie. 2014 Sep:104:90-9. doi: 10.1016/j.biochi.2014.05.010. Epub 2014 Jun 6.

Abstract

Many human proteins have a modular design with receptor and structural domains. Using adhesion/growth-regulatory galectin-3 as model, we describe an interdisciplinary strategy to define the functional significance of its tail established by nine non-triple helical collagen-like repeats (I-IX) and the N-terminal peptide. Genetic engineering with sophisticated mass spectrometric product analysis provided the tools for biotesting, i.e. eight protein variants with different degrees of tail truncation. Evidently,various aspects of galectin-3 activity (cis binding and cell bridging) are affected by tail shortening in a different manner. Thus, this combined approach reveals an unsuspected complexity of structure-function relationship, encouraging further application beyond this chimera-type galectin.

Keywords: Adhesion; Glycoprotein; Lectin; Matrix metalloproteinase; Neuroblastoma; Proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Adhesion
  • Cell Aggregation
  • Cell Proliferation
  • Cricetinae
  • Galectin 1 / metabolism*
  • Galectin 3 / chemistry*
  • Galectin 3 / genetics
  • Galectin 3 / metabolism*
  • Glycoproteins / metabolism*
  • Humans
  • Molecular Sequence Data
  • Mutation
  • Neuroblastoma / pathology*
  • Protein Binding
  • Protein Engineering
  • Rats
  • Recombinant Proteins / chemistry*
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism*

Substances

  • Galectin 1
  • Galectin 3
  • Glycoproteins
  • Recombinant Proteins