Lectinology 4.0: Altering modular (ga)lectin display for functional analysis and biomedical applications

• Published in: Biochimica et biophysica acta. General subjects Vol. 1863; no. 5; pp. 935 - 940
• Main Authors: Ludwig, Anna-Kristin, Kaltner, Herbert, Kopitz, Jürgen, Gabius, Hans-Joachim
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.05.2019
• Subjects: Cell adhesion; galectins; Glycoconjugate; humans; Lectin; Mutagenesis; polysaccharides; structure-activity relationships; Sugar code; Lectin; Sugar code; Glycoconjugate; Mutagenesis; Cell adhesion
• ISSN: 0304-4165; 1872-8006; 1872-8006
• DOI: 10.1016/j.bbagen.2019.03.005

Recognition of glycans by lectins is emerging as (patho)physiologically broadly used mode of cellular information transfer. Whereas the direct ligand-receptor contact is often already thoroughly characterized, the functional relevance of aspects of architecture such as modular design and valence of lectins is less well defined. Following an introduction to modular lectin design, three levels of methodology are then reviewed that delineate lectin structure-activity relationships beyond glycan binding, with emphasis on domain shuffling. Engineering of variants by modular transplantation facilitates versatile Nature-inspired design switches and access to new combinations with translational potential, as exemplified for human adhesion/growth-regulatory galectins. To gain an understanding of the functional significance of natural variations in quaternary structure and modular design within a protein family is a current challenge. Strategic application of methods of the described phases is a means to respond to this challenge. •Lectins have distinct types of design of not yet known functional significance.•Chemical modifications are a means to alter quaternary structure and cross-linking.•Site-specific sequence changes generate lectins with new specificity.•Modular transplantations generate lectin variants with new design and function.•Human lectin variants have innovative potential for therapy.