Abstract
Among members of the family of adhesion/growth-regulatory galectins, galectin-3 (Gal-3) bears a unique modular architecture. A N-terminal tail (NT) consisting of the N-terminal segment (NTS) and nine collagen-like repeats is linked to the canonical lectin domain. In contrast to bivalent proto- and tandem-repeat-type galectins, Gal-3 is monomeric in solution, capable to self-associate in the presence of bi- to multivalent ligands, and the NTS is involved in cellular compartmentalization. Since no crystallographic information on Gal-3 beyond the lectin domain is available, we used a shortened variant with NTS and repeats VII-IX. This protein crystallized as tetramers with contacts between the lectin domains. The region from Tyr101 (in repeat IX) to Leu114 (in the CRD) formed a hairpin. The NTS extends the canonical β-sheet of F1-F5 strands with two new β-strands on the F face. Together, crystallographic and SAXS data reveal a mode of intramolecular structure building involving the highly flexible Gal-3’s NT.
Highlights
The functional pairing of cellular glycoconjugates with tissue lectins is giving the unsurpassed structural variability of lipid/protein-linked glycans a physiological meaning[1]
The detailed crystallographic data of ordered regions within the N-terminal tail (NT) of the Gal-3[N-terminal stretch (NTS)/VII-IX] protein became possible. This accomplishment led to a structural model that was set in relation to the experimentally determined shape in comparative small angle X-ray scattering (SAXS) studies of this protein, together with full-length Gal-3 and the variant with repeats IV-IX in its NT (Gal-3[NTS/IV-IX])
Gal-3[NTS/VII-IX] at 2.2 Å resolution indicated the presence of 12 monomers in the asymmetric unit
Summary
The functional pairing of cellular glycoconjugates with tissue lectins is giving the unsurpassed structural variability of lipid/protein-linked glycans a physiological meaning[1]. The detailed crystallographic data of ordered regions within the NT of the Gal-3[NTS/VII-IX] protein (for sequence details, please see Supplementary Fig. S1) became possible This accomplishment led to a structural model that was set in relation to the experimentally determined shape in comparative small angle X-ray scattering (SAXS) studies of this protein, together with full-length Gal-3 and the variant with repeats IV-IX in its NT (Gal-3[NTS/IV-IX]). When combined, these investigations disclosed a conformation of two regions of the highly flexible NT seen in the crystal of Gal-3[NTS/VII-IX] and the overall shape of the three proteins in solution. The obtained data enabled us to suggest a molecular pattern of contacts favoring the formation of aggregates of Gal-3 into a tetramer under the given conditions driven by CRD-CRD interactions
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
