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dc.contributor.authorLudwig, Anna-Kristin
dc.contributor.authorMichalak, Malwina
dc.contributor.authorXiao, Qi
dc.contributor.authorGilles, Ulrich
dc.contributor.authorMedrano, Francisco J
dc.contributor.authorMa, Hanyue
dc.contributor.authorFitzGerald, Forrest G
dc.contributor.authorHasley, William D
dc.contributor.authorMelendez-Davila, Adriel
dc.contributor.authorLiu, Matthew
dc.contributor.authorRahimi, Khosrow
dc.contributor.authorKostina, Nina Yu
dc.contributor.authorRodriguez-Emmenegger, Cesar
dc.contributor.authorMöller, Martin
dc.contributor.authorLindner, Ingo
dc.contributor.authorKaltner, Herbert
dc.contributor.authorCudic, Mare
dc.contributor.authorReusch, Dietmar
dc.contributor.authorKopitz, Jürgen
dc.contributor.authorRomero, Antonio
dc.contributor.authorOscarson, Stefan
dc.contributor.authorKlein, Michael L
dc.contributor.authorGabius, Hans-Joachim
dc.contributor.authorPercec, Virgil
dc.date.accessioned2020-02-10T14:27:00Z
dc.date.available2020-02-10T14:27:00Z
dc.date.issued2019-02-04
dc.identifier.pmid30718416
dc.identifier.doi10.1073/pnas.1813515116
dc.identifier.urihttp://hdl.handle.net/10147/627163
dc.descriptionGlycan-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.en_US
dc.description.abstractGlycan-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.
dc.language.isoenen_US
dc.rightsCopyright © 2019 the Author(s). Published by PNAS.
dc.subjectglycoconjugateen_US
dc.subjectlectinen_US
dc.subjectparasiteen_US
dc.subjecttumoren_US
dc.subjectCELL BIOLOGYen_US
dc.subjectMOLECULAR BIOLOGYen_US
dc.titleDesign-functionality relationships for adhesion/growth-regulatory galectins.en_US
dc.typeArticleen_US
dc.identifier.eissn1091-6490
dc.identifier.journalProceedings of the National Academy of Sciences of the United States of Americaen_US
dc.source.journaltitleProceedings of the National Academy of Sciences of the United States of America
dc.source.volume116
dc.source.issue8
dc.source.beginpage2837
dc.source.endpage2842
refterms.dateFOA2020-02-10T14:27:01Z
dc.source.countryUnited States
dc.source.countryUnited States


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