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Göteborgs universitets publikationer

Mutational tuning of galectin-3 specificity and biological function.

Författare och institution:
Emma Salomonsson (-); Michael C Carlsson (-); Veronica Osla (Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning); Ruth Hendus-Altenburger (-); Barbro Kahl Knutson (-); Christopher T Oberg (-); Anders Sundin (-); Rickard Nilsson (-); Eva Nordberg-Karlsson (-); Ulf J Nilsson (-); Anna Karlsson (Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning); James M Rini (-); Hakon Leffler (-)
Publicerad i:
The Journal of biological chemistry, 285 s. 35079-35091
Artikel, refereegranskad vetenskaplig
Sammanfattning (abstract):
Galectins are defined by a conserved beta-galactoside binding site, which has been linked to many of their important functions in e.g. cell adhesion, signaling and intracellular trafficking. Weak adjacent sites may enhance or decrease affinity for natural beta-galactoside containing glycoconjugates, but little is known about the biological role of this modulation of affinity (fine specificity). We have now produced 10 mutants of human galectin-3, with changes in these adjacent sites, which have altered carbohydrate-binding fine specificity but which retain the basic beta-galactoside binding activity as show by glycan-array binding and a solution-based fluorescence anisotropy assay. Each mutant was also tested in two biological assays to provide a correlation between fine specificity and function. Galectin-3 R186S, which has selectively lost affinity for LacNAc, a disaccharide moiety commonly found on glycoprotein glycans, has lost the ability to activate neutrophil leukocytes and intracellular targeting into vesicles. K176L has increased affinity for beta-galactosides substituted with GlcNAcbeta1-3 as found in poly-N-acetyllactosaminoglycans, and increased potency to activate neutrophil leukocytes, even though it has lost other aspects of galectin-3 fine specificity. G182A has altered carbohydrate-binding fine specificity and altered intracellular targeting into vesicles, a possible link to the intracellular galectin-3-mediated anti-apoptotic effect known to be lost by this mutant. Finally, the mutants have helped to define the differences in fine specificity shown by Xenopus, mouse and human galectin-3 and as such, evidence for adaptive change during evolution.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
Biologiska vetenskaper ->
Biokemi och molekylärbiologi ->
Cell- och molekylärbiologi
Amino Acid Substitution, Animals, Galactosides, genetics, metabolism, Galectin 3, genetics, metabolism, pharmacology, Humans, Mice, Mutation, Missense, Neutrophil Activation, drug effects, physiology, Neutrophils, metabolism, Substrate Specificity, Xenopus laevis
Postens nummer:
Posten skapad:
2010-09-26 09:15
Posten ändrad:
2011-11-15 11:43

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