Structural Basis Underlying the Binding Preference of Human Galectins-1, -3 and -7 for Galβ1-3/4GlcNAc

Galectins represent β-galactoside-binding proteins and are known to bind Galβ1-3/4GlcNAc disaccharides (abbreviated as LN1 and LN2, respectively). Despite high sequence and structural homology shared by the carbohydrate recognition domain (CRD) of all galectin members, how each galectin displays dif...

Full description

Saved in:
Bibliographic Details
Published in:PloS one 2015-05, Vol.10 (5), p.e0125946-e0125946
Main Authors: Hsieh, Tung-Ju, Lin, Hsien-Ya, Tu, Zhijay, Huang, Bo-Shun, Wu, Shang-Chuen, Lin, Chun-Hung
Format: Article
Language:English
Subjects:
Antigens
Binding
Biosensors
Bridge maintenance
Carbohydrates
Cell adhesion & migration
Chemistry
Crystallography, X-Ray
Disaccharides
Disaccharides - chemistry
Disaccharides - metabolism
Galactosides - chemistry
Galactosides - metabolism
Galectin 1 - metabolism
Galectin 3 - metabolism
Galectins - metabolism
Homology
Humans
Interferometry
Kinases
Ligands
Next-generation sequencing
Preferences
Protein Binding
Proteins
Salts
Sugar
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Galectins represent β-galactoside-binding proteins and are known to bind Galβ1-3/4GlcNAc disaccharides (abbreviated as LN1 and LN2, respectively). Despite high sequence and structural homology shared by the carbohydrate recognition domain (CRD) of all galectin members, how each galectin displays different sugar-binding specificity still remains ambiguous. Herein we provided the first structural evidence of human galectins-1, 3-CRD and 7 in complex with LN1. Galectins-1 and 3 were shown to have higher affinity for LN2 than for LN1, while galectin-7 displayed the reversed specificity. In comparison with the previous LN2-complexed structures, the results indicated that the average glycosidic torsion angle of galectin-bound LN1 (ψ(LN1) ≈ 135°) was significantly differed from that of galectin-bound LN2 (ψ(LN2 )≈ -108°), i.e. the GlcNAc moiety adopted a different orientation to maintain essential interactions. Furthermore, we also identified an Arg-Asp/Glu-Glu-Arg salt-bridge network and the corresponding loop (to position the second Asp/Glu residue) critical for the LN1/2-binding preference.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0125946