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The Human Lectin Galectin‐3 Recognizes Chondroitin Sulfate Proteoglycans (CSPGs) and Sulfated Glycosaminoglycans
Author(s) -
Dam Tarun,
Talaga Melanie,
Fan Ni,
Fueri Ashli,
Brown Robert,
Bandyopadhyay Purnima
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.784.8
Subject(s) - sulfation , chondroitin sulfate , chemistry , chondroitin , dermatan sulfate , glycan , glycosaminoglycan , biochemistry , proteoglycan , decorin , lectin , heparin , extracellular matrix , plasma protein binding , heparan sulfate , glycoprotein
Glycan‐binding proteins are classified in two major but distinct groups: lectins and glycosaminoglycan (GAG)‐binding proteins (GAGBPs). The multifunctional human lectin galectin‐3 (Gal‐3) is a member of the first group. GAGBPs, on the other hand, include a variety of non‐lectin proteins such as growth factors, cytokines, morphogens and ECM (extracellular matrix) proteins. The general structures of the binding sites of lectins, their preferred glycan structures and their mode of action are fundamentally different from those of GAGBPs. A member of one group rarely possesses the characteristics of both groups. Our data, however, show that Gal‐3 is a notable exception to that rule. In the present study, we report several significant findings. First, calorimetric and spectroscopic data show for the first time that Gal‐3 behaves like a GAGBP. The lectin interacts with unmodified sulfated GAGs (heparin and chondroitin sulfates) and chondroitin sulfate proteoglycans (CSPGs) at physiological pH and NaCl concentration. Second, the binding of sulfated GAGs and CSPGs to Gal‐3 is not a result of non‐specific interactions, rather sulfated GAGs and CSPGs specifically bind to Gal‐3, apparently, via the LacNAc/lactose binding site of Gal‐3. Finally, while heparin and chondroitin sulfate B (dermatan sulfate) are found to be monovalent ligands of Gal‐3, chondroitin sulfate A (CSA), chondroitin sulfate C (CSC) and bovine CSPG engage in multivalent binding with Gal‐3. Such multivalent binding leads to the formation of noncovalent cross‐linked complexes, which is reversible by lactose and different sulfated GAGs. Hill plot analysis of calorimetric data show that the binding of CSA, CSC and bovine CSPG to Gal‐3 is associated with progressive negative cooperativity effects. The present study provides a foundation for discovering new functions of GAGs and CSPGs mediated by Gal‐3 [1]. Support or Funding Information National Science FoundationMichigan Technological University