Reading a glycocode - mechanism and function of galectin-glycan interactions

Emma Salomonsson

Research output: ThesisDoctoral Thesis (compilation)


There is an intensive interest in characterising the structure and function of galectins, which is not surprising given their many important cellular functions and strong implications in human disease. Understanding the mechanisms involved in galectin functions will help to find selective and novel strategies for disease treatment and diagnosis. A key to this lies in their carbohydrate binding specificity and the multivalent effects taking place on a cell surface in their presence. The aim of this thesis was to deepen our understanding of galectin recognition and correlate it to biological function.
In paper I we altered the fine specificity of galectin-3 using site directed mutagenesis, and evaluated the effect of this in two biological systems: the ability of extracellular galectin-3 to activate neutrophil leucocytes and intracellular galectin-3 to direct intracellular targeting. A clear correlation was found between fine specificity, as measured with glycan array and fluorescence anisotropy, and biological activity. The most striking effect was the total loss of affinity for the galectin-3 preferred ligand LacNAc when substituting Arg186 to Ser or Ile; these mutants were incompetent in binding and activating neutrophils, and did not enter intracellular vesicles. Galectin-1 does not have the same multifaceted binding specificity as galectin-3. However, its ability to cross-link cell surface receptors has been shown to be of great importance for biological function. In paper II, we therefore analysed the role of galectin-1 dimerisation in high affinity ligand binding using a mutant with strongly reduced ability to form dimers. Surprisingly, high affinity binding of small synthetic divalent ligands as well as multivalent ligands, such as asialofetuin and serum glycoproteins, did not depend much on the dimeric state of galectin-1, but was instead mainly due to added weak interactions within the same carbohydrate recognition domain. In paper III, we studied the modulating effect of the synthetic anti-angiogenic peptide anginex that has been shown to interact with galectin-1, and found that it greatly enhanced the affinity of galectin-1 for various glycoproteins. This raises the question if there is a natural counterpart to anginex in vivo.
Original languageEnglish
Awarding Institution
  • Division of Microbiology, Immunology and Glycobiology - MIG
  • Leffler, Hakon, Supervisor
  • Gullberg, Urban, Supervisor
  • Nilsson, Ulf, Supervisor
Award date2011 Apr 15
ISBN (Print)978-91-86671-78-5
Publication statusPublished - 2011

Bibliographical note

Defence details

Date: 2011-04-15
Time: 09:00
Place: Segerfalksalen, BMC Neurocentrum, Sölvegatan 17, Lund

External reviewer(s)

Name: Clausen, Henrik
Title: [unknown]
Affiliation: Copenhagen Center for Glycomics, Department of Cellular and Molecular Medicine, University of Copenhagen, Denmark


Subject classification (UKÄ)

  • Microbiology in the medical area
  • Immunology in the medical area

Free keywords

  • galectin
  • specificity
  • affinity
  • multivalency
  • fluorescence anisotropy
  • glycan array
  • serum glycoproteins
  • anginex


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