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Monovalent Interactions of Galectin-1

Salomonsson, Emma LU ; Larumbe, Amaia; Tejler, Johan LU ; Tullberg, Erik LU ; Rydberg, Hanna; Sundin, Anders LU ; Khabut, Areej LU ; Frejd, Torbjörn LU ; Lobsanov, Yuri and Rini, James M., et al. (2010) In Biochemistry 49(44). p.9518-9532
Abstract
Galectin-1, beta-galactoside binding lectin involved in immunoregulation and cancer, binds natural and many synthetic multivalent glycoconjugates with an apparent glycoside cluster effect, that is, affinity above and beyond what would be expected from the concentration of the determinant sugar. Here we have analyzed the mechanism of such cluster effects in solution at physiological concentration using a fluorescence anisotropy assay with a novel fluorescent high-affinity galectin-1 binding probe. The interaction of native dimeric and monomeric mutants of rat and human galectin-1 with mono- and divalent small molecules, fetuin, asialofetuin, and human serum glycoproteins was analyzed. Surprisingly, high-affinity binding did not depend much... (More)
Galectin-1, beta-galactoside binding lectin involved in immunoregulation and cancer, binds natural and many synthetic multivalent glycoconjugates with an apparent glycoside cluster effect, that is, affinity above and beyond what would be expected from the concentration of the determinant sugar. Here we have analyzed the mechanism of such cluster effects in solution at physiological concentration using a fluorescence anisotropy assay with a novel fluorescent high-affinity galectin-1 binding probe. The interaction of native dimeric and monomeric mutants of rat and human galectin-1 with mono- and divalent small molecules, fetuin, asialofetuin, and human serum glycoproteins was analyzed. Surprisingly, high-affinity binding did not depend much on the dimeric state of galectin-1 and thus is due mainly to monomeric interactions of a single carbohydrate recognition domain. The mechanism for this is unknown, but one possibility includes additional interactions that high-affinity ligands make with an extended binding site on the carbohydrate recognition domain, It follows that such weak additional interactions must be important for the biological function of galectin-1 and also for the design of galectin-1 inhibitors. (Less)
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type
Contribution to journal
publication status
published
subject
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Biochemistry
volume
49
issue
44
pages
9518 - 9532
publisher
The American Chemical Society
external identifiers
  • wos:000283624500011
  • scopus:78149325767
ISSN
0006-2960
DOI
10.1021/bi1009584
language
English
LU publication?
yes
id
703fd138-6555-47fd-941a-2d8c013ad196 (old id 1753445)
date added to LUP
2011-01-04 08:14:07
date last changed
2018-05-29 09:36:53
@article{703fd138-6555-47fd-941a-2d8c013ad196,
  abstract     = {Galectin-1, beta-galactoside binding lectin involved in immunoregulation and cancer, binds natural and many synthetic multivalent glycoconjugates with an apparent glycoside cluster effect, that is, affinity above and beyond what would be expected from the concentration of the determinant sugar. Here we have analyzed the mechanism of such cluster effects in solution at physiological concentration using a fluorescence anisotropy assay with a novel fluorescent high-affinity galectin-1 binding probe. The interaction of native dimeric and monomeric mutants of rat and human galectin-1 with mono- and divalent small molecules, fetuin, asialofetuin, and human serum glycoproteins was analyzed. Surprisingly, high-affinity binding did not depend much on the dimeric state of galectin-1 and thus is due mainly to monomeric interactions of a single carbohydrate recognition domain. The mechanism for this is unknown, but one possibility includes additional interactions that high-affinity ligands make with an extended binding site on the carbohydrate recognition domain, It follows that such weak additional interactions must be important for the biological function of galectin-1 and also for the design of galectin-1 inhibitors.},
  author       = {Salomonsson, Emma and Larumbe, Amaia and Tejler, Johan and Tullberg, Erik and Rydberg, Hanna and Sundin, Anders and Khabut, Areej and Frejd, Torbjörn and Lobsanov, Yuri and Rini, James M. and Nilsson, Ulf and Leffler, Hakon},
  issn         = {0006-2960},
  language     = {eng},
  number       = {44},
  pages        = {9518--9532},
  publisher    = {The American Chemical Society},
  series       = {Biochemistry},
  title        = {Monovalent Interactions of Galectin-1},
  url          = {http://dx.doi.org/10.1021/bi1009584},
  volume       = {49},
  year         = {2010},
}