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Intra- and inter-molecular interactions of human galectin-3: assessment by full-assignment-based NMR.

Ippel, Hans ; Miller, Michelle C ; Vértesy, Sabine ; Zhang, Yi ; Cañada, F Javier ; Suylen, Dennis ; Umemoto, Kimiko ; Romanò, Cecilia ; Hackeng, Tilman and Tai, Guihua , et al. (2016) In Glycobiology 26(8). p.888-903
Abstract
Galectin-3 is an adhesion/growth-regulatory protein with a modular design comprising an N-terminal tail (NT, residues 1-111) and the conserved carbohydrate recognition domain (CRD, residues 112-250). The chimera-type galectin interacts with both glycan and peptide motifs. Complete (13)C/(15)N-assignment of the human protein makes NMR-based analysis of its structure beyond the CRD possible. Using two synthetic NT polypeptides covering residues 1-50 and 51-107, evidence for transient secondary structure was found with helical conformation from residues 5 to 15 as well as proline-mediated, multi-turn structure from residues 18 to 32 and around PGAYP repeats. Intramolecular interactions occur between the CRD F-face (the 5-stranded β-sheet... (More)
Galectin-3 is an adhesion/growth-regulatory protein with a modular design comprising an N-terminal tail (NT, residues 1-111) and the conserved carbohydrate recognition domain (CRD, residues 112-250). The chimera-type galectin interacts with both glycan and peptide motifs. Complete (13)C/(15)N-assignment of the human protein makes NMR-based analysis of its structure beyond the CRD possible. Using two synthetic NT polypeptides covering residues 1-50 and 51-107, evidence for transient secondary structure was found with helical conformation from residues 5 to 15 as well as proline-mediated, multi-turn structure from residues 18 to 32 and around PGAYP repeats. Intramolecular interactions occur between the CRD F-face (the 5-stranded β-sheet behind the canonical carbohydrate-binding 6-stranded β-sheet of the S-face) and NT in full-length galectin-3, with the sequence P(23)GAW(26) … P(37)GASYPGAY(45) defining the primary binding epitope within the NT. Work with designed peptides indicates that the PGAX motif is crucial for self-interactions between NT/CRD. Phosphorylation at position Ser6 (and Ser12) (a physiological modification) and the influence of ligand binding have minimal effect on this interaction. Lastly, galectin-3 molecules can interact weakly with each other via the F-faces of their CRDs, an interaction that appears to be assisted by their NTs. Overall, our results add insight to defining binding sites on galectin-3 beyond the canonical contact area for β-galactosides. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Glycobiology
volume
26
issue
8
pages
16 pages
publisher
Oxford University Press
external identifiers
  • pmid:26911284
  • pmid:26911284
  • scopus:84988535559
ISSN
1460-2423
DOI
10.1093/glycob/cww021
language
English
LU publication?
yes
id
cb8fd38f-9f6c-4249-adf4-08020a03552f (old id 8821758)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/26911284?dopt=Abstract
date added to LUP
2016-04-04 09:14:35
date last changed
2022-03-31 01:47:19
@article{cb8fd38f-9f6c-4249-adf4-08020a03552f,
  abstract     = {{Galectin-3 is an adhesion/growth-regulatory protein with a modular design comprising an N-terminal tail (NT, residues 1-111) and the conserved carbohydrate recognition domain (CRD, residues 112-250). The chimera-type galectin interacts with both glycan and peptide motifs. Complete (13)C/(15)N-assignment of the human protein makes NMR-based analysis of its structure beyond the CRD possible. Using two synthetic NT polypeptides covering residues 1-50 and 51-107, evidence for transient secondary structure was found with helical conformation from residues 5 to 15 as well as proline-mediated, multi-turn structure from residues 18 to 32 and around PGAYP repeats. Intramolecular interactions occur between the CRD F-face (the 5-stranded β-sheet behind the canonical carbohydrate-binding 6-stranded β-sheet of the S-face) and NT in full-length galectin-3, with the sequence P(23)GAW(26) … P(37)GASYPGAY(45) defining the primary binding epitope within the NT. Work with designed peptides indicates that the PGAX motif is crucial for self-interactions between NT/CRD. Phosphorylation at position Ser6 (and Ser12) (a physiological modification) and the influence of ligand binding have minimal effect on this interaction. Lastly, galectin-3 molecules can interact weakly with each other via the F-faces of their CRDs, an interaction that appears to be assisted by their NTs. Overall, our results add insight to defining binding sites on galectin-3 beyond the canonical contact area for β-galactosides.}},
  author       = {{Ippel, Hans and Miller, Michelle C and Vértesy, Sabine and Zhang, Yi and Cañada, F Javier and Suylen, Dennis and Umemoto, Kimiko and Romanò, Cecilia and Hackeng, Tilman and Tai, Guihua and Leffler, Hakon and Kopitz, Jürgen and André, Sabine and Kübler, Dieter and Jiménez-Barbero, Jesús and Oscarson, Stefan and Gabius, Hans-Joachim and Mayo, Kevin H}},
  issn         = {{1460-2423}},
  language     = {{eng}},
  month        = {{02}},
  number       = {{8}},
  pages        = {{888--903}},
  publisher    = {{Oxford University Press}},
  series       = {{Glycobiology}},
  title        = {{Intra- and inter-molecular interactions of human galectin-3: assessment by full-assignment-based NMR.}},
  url          = {{http://dx.doi.org/10.1093/glycob/cww021}},
  doi          = {{10.1093/glycob/cww021}},
  volume       = {{26}},
  year         = {{2016}},
}