Fine-tuning of prototype chicken galectins: structure of CG-2 and structure–activity correlations

37 p-.8 fig.-3 tab.
The comparatively small number of members of the family of adhesion/growth-regulatory galectins in chicken predestines this system as an attractive model to study divergence of these lectins after gene duplications. Expression profiling of the three homodimeric (proto-type) chicken galectins (CG-1A, CG-1B and CG-2) has raised evidence for distinct functionalities, explaining the interest in a detailed crystallographic analysis of CG-2. As revealed here, marked differences are found in the ligand-binding site and in the contact pattern within the homodimer interface, underlying a characteristic orientation of the two subunits. Notably, a distinctive trimer of dimers that is unique in all galectin crystal structures reported to date forms the core unit of the crystallographic assembly. Combination with spectroscopic and thermodynamic measurements, and comparisons with CG-1A and CG-1B, identifies differential changes in circular-dichroism spectra in the presence of lactose, reflecting the far-reaching impact of the ligand on hydrodynamic behavior, and inter-galectin differences in both the entropy and the enthalpy of binding. This structural information is a salient step to complete the analysis of the full set of galectins from this model organism.
This work has been kindly supported by grants BFU2009-10052, BFU2011-24615, BFU2012-36825 and CSD2009-00088 from the Spanish Ministry of Science and Innovation, the CIBER of Respiratory Diseases (CIBERES), an initiative from ISCIII, the Regional Government of Madrid (S2010/BMD-2353), and funding from the European Union’s Seventh Framework Program FP7/2007-2013 under REA grant agreements no. 260600 (“GlycoHIT”) and 317297 (“GLYCOPHARM”).