Structural significance of galectin design: impairment of homodimer stability by linker insertion and partial reversion by ligand presence

Protein Engineering, Design & Selection : PEDS
Sabine VértesyHans-Joachim Gabius

Abstract

Lectins translate information encoded in glycan chains of cellular glycoconjugates into bioeffects. The topological presentation of contact sites for cognate sugar binding is a crucial factor toward this end. To dissect the significance of such phylogenetically conserved properties, the design and engineering of non-natural variants are attractive approaches. Here, a homodimeric human lectin, i.e. adhesion/growth-regulatory galectin-1, is converted into a tandem-repeat display by introducing the 33-amino-acid linker of another family member (i.e. galectin-8). The yield of variant was reduced by about a third. This protein had ∼10-fold higher activity in hemagglutination. Nearly complete sequence determination by mass-spectrometric in-source decay and fingerprinting excluded the presence of any modifications. When (1)H-(15)N heteronuclear single-quantum coherence data on the (15)N-labeled variant and wild-type protein were compared, changes in chemical shifts, signal intensities and resonance multiplicities revealed reduction of stability of interfacial contacts between the lectin domains and an increase in inter-domain flexibility. When both binding sites in the variant were loaded with ligand, association of the two carbohydra...Continue Reading

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Citations

Apr 23, 2015·Proceedings of the National Academy of Sciences of the United States of America·Shaodong ZhangVirgil Percec
Mar 10, 2016·Cellular and Molecular Life Sciences : CMLS·H-J GabiusH Kaltner
Mar 8, 2016·Expert Opinion on Therapeutic Patents·Helen BlanchardXing Yu
Dec 25, 2016·Histochemistry and Cell Biology·Herbert KaltnerHans-Joachim Gabius
Sep 20, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Anna-Kristin LudwigHans-Joachim Gabius
Apr 5, 2018·Proceedings of the National Academy of Sciences of the United States of America·Carlos A OrozcoPilar Navarro
Feb 23, 2020·EMBO Reports·Veit EckardtKevin H Mayo
Dec 26, 2016·Histochemistry and Cell Biology·René RoyHans-Joachim Gabius
Feb 6, 2019·Proceedings of the National Academy of Sciences of the United States of America·Anna-Kristin LudwigVirgil Percec
Jun 22, 2021·Histochemistry and Cell Biology·Anna-Kristin LudwigHans-Joachim Gabius

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