How altering the modular architecture affects aspects of lectin activity: case study on human galectin-1. (15th May 2019)

• Record Type: Journal Article
• Authors: Kutzner, Tanja J; Gabba, Adele; FitzGerald, Forrest G; Shilova, Nadezhda V; García Caballero, Gabriel; Ludwig, Anna-Kristin; Manning, Joachim C; Knospe, Clemens; Kaltner, Herbert; Sinowatz, Fred; Murphy, Paul V; Cudic, Mare; Bovin, Nicolai V; Gabius, Hans-Joachim
• Is Part Of: Glycobiology. Volume 29:Number 8(2019)
• Page Start: 593
• Page End: 607
• Publication Date: 2019-05-15
• Subjects: calorimetry -- glycan -- histochemistry -- lectin -- sugar code; Glycoproteins -- Periodicals; Glycolipids -- Periodicals; Glycoconjugates -- Periodicals; 572.567
• DOI: 10.1093/glycob/cwz034
• Languages: English
• ISSNs: 0959-6658

Abstract

Abstract: Discoveries on involvement of glycan–protein recognition in many (patho)physiological processes are directing attention to exploring the significance of a fundamental structural aspect of sugar receptors beyond glycan specificity, i.e., occurrence of distinct types of modular architecture. In order to trace clues for defining design–functionality relationships in human lectins, a lectin's structural unit has been used as source material for engineering custom-made variants of the wild-type protein. Their availability facilitates comparative analysis toward the stated aim. With adhesion/growth-regulatory human galectin-1 as example, the strategy of evaluating how changes of its design (here, from the homodimer of non-covalently associated domains to (i) linker-connected di- and tetramers and (ii) a galectin-3-like protein) affect activity is illustrated by using three assay systems of increasing degree of glycan complexity. Whereas calorimetry with two cognate disaccharides and array testing with 647 (glyco)compounds disclosed no major changes, galectin histochemical staining profiles of tissue sections that present natural glycome complexity revealed differences between wild-type and linker-connected homo-oligomers as well as between the galectin-3-like variant and wild-type galectin-3 for cell-type positivity, level of intensity at the same site and susceptibility for inhibition by a bivalent glycocompound. These results underscore the strength of the documented approach. Moreover, they give direction to proceed to (i) extending its application to other members of this lectin family, especially galectin-3 and (ii) then analyzing impact of architectural alterations on cell surface lattice formation and ensuing biosignaling systematically, considering the variants' potential for translational medicine.