Design-functionality relationships for adhesion/growth-regulatory galectins
Glycan-lectin recognition is assumed to elicit its broad range of (patho)physiological functions via a combination of specific contact formation with generation of complexes of distinct signal-triggering topology on biomembranes. Faced with the challenge to understand why evolution has led to three...
Saved in:
| Main Authors: | , , |
|---|---|
| Format: | Article (Journal) |
| Language: | English |
| Published: |
February 4, 2019
|
| In: |
Proceedings of the National Academy of Sciences of the United States of America
Year: 2019, Volume: 116, Issue: 8, Pages: 2837-2842 |
| ISSN: | 1091-6490 |
| DOI: | 10.1073/pnas.1813515116 |
| Online Access: | Verlag, Volltext: https://doi.org/10.1073/pnas.1813515116 Verlag, Volltext: https://www.pnas.org/content/116/8/2837 
|
| Author Notes: | Anna-Kristin Ludwig, Malwina Michalak, Qi Xiao, Ulrich Gilles, Francisco J. Medrano, Hanyue Ma, Forrest G. FitzGerald, William D. Hasley, Adriel Melendez-Davila, Matthew Liu, Khosrow Rahimi, Nina Yu Kostina, Cesar Rodriguez-Emmenegger, Martin Möller, Ingo Lindner, Herbert Kaltner, Mare Cudic, Dietmar Reusch, Jürgen Kopitz, Antonio Romero, Stefan Oscarson, Michael L. Klein, Hans-Joachim Gabius, and Virgil Percec |
| Summary: | Glycan-lectin recognition is assumed to elicit its broad range of (patho)physiological functions via a combination of specific contact formation with generation of complexes of distinct signal-triggering topology on biomembranes. Faced with the challenge to understand why evolution has led to three particular modes of modular architecture for adhesion/growth-regulatory galectins in vertebrates, here we introduce protein engineering to enable design switches. The impact of changes is measured in assays on cell growth and on bridging fully synthetic nanovesicles (glycodendrimersomes) with a chemically programmable surface. Using the example of homodimeric galectin-1 and monomeric galectin-3, the mutual design conversion caused qualitative differences, i.e., from bridging effector to antagonist/from antagonist to growth inhibitor and vice versa. In addition to attaining proof-of-principle evidence for the hypothesis that chimera-type galectin-3 design makes functional antagonism possible, we underscore the value of versatile surface programming with a derivative of the pan-galectin ligand lactose. Aggregation assays with N,N′-diacetyllactosamine establishing a parasite-like surface signature revealed marked selectivity among the family of galectins and bridging potency of homodimers. These findings provide fundamental insights into design-functionality relationships of galectins. Moreover, our strategy generates the tools to identify biofunctional lattice formation on biomembranes and galectin-reagents with therapeutic potential. |
|---|---|
| Item Description: | Gesehen am 26.07.2019 |
| Physical Description: | Online Resource |
| ISSN: | 1091-6490 |
| DOI: | 10.1073/pnas.1813515116 |