Adhesion/growth-regulatory galectins tested in combination: evidence for formation of hybrids as heterodimers

Michelle C. Miller, Anna-Kristin Ludwig, Kanin Wichapong, Herbert Kaltner, Juergen Kopitz, Hans-Joachim Gabius, Kevin H. Mayo*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

28 Citations (Web of Science)

Abstract

The delineation of the physiological significance of protein (lectin)-glycan recognition and the structural analysis of individual lectins have directed our attention to studying them in combination. In this report, we tested the hypothesis of hybrid formation by using binary mixtures of homodimeric galectin-1 and -7 as well as a proteolytically truncated version of chimera-type galectin-3. Initial supportive evidence is provided by affinity chromatography using resin-presented galectin-7. Intriguingly, the extent of cell binding by cross-linking of surface counter-receptor increased significantly for monomeric galectin-3 form by the presence of galectin-1 or -7. Pulsed-field gradient NMR (nuclear magnetic resonance) diffusion measurements on these galectin mixtures indicated formation of heterodimers as opposed to larger oligomers. N-15-H-1 heteronuclear single quantum coherence NMR spectroscopy and molecular dynamics simulations allowed us to delineate how different galectins interact in the heterodimer. The possibility of domain exchange between galectins introduces a new concept for understanding the spectrum of their functionality, particularly when these effector molecules are spatially and temporally co-expressed as found in vivo.
Original languageEnglish
Pages (from-to)1003-1018
Number of pages16
JournalBiochemical Journal
Volume475
Issue number5
DOIs
Publication statusPublished - 15 Mar 2018

Keywords

  • CHEMICAL-SHIFT ASSIGNMENTS
  • HUMAN NEUROBLASTOMA-CELLS
  • CARBOHYDRATE-RECOGNITION DOMAIN
  • PANCREATIC-CARCINOMA MODEL
  • CHIMERA-TYPE GALECTIN-3
  • MOLECULAR-DYNAMICS
  • P53-INDUCED GENE-1
  • N-15 BACKBONE
  • IN-VITRO
  • DIFFUSION MEASUREMENTS

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