3AYA

Crystal structure of galectin-3 CRD domian complexed with Thomsen-Friedenreich antigen

3AYA の概要

• エントリーDOI: 10.2210/pdb3aya/pdb
• 関連するPDBエントリー: 3AYC 3AYD 3AYE
• 関連するBIRD辞書のPRD_ID: PRD_900084
• 分子名称: Galectin-3, beta-D-galactopyranose-(1-3)-2-acetamido-2-deoxy-alpha-D-galactopyranose, THREONINE, ... (5 entities in total)
• 機能のキーワード: rossmann fold, a beta-galactose-binding protein, beta-galactosides, cell-surface, nuclear, sugar binding protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 32016.43

構造登録者

Bian, C.F.,Li, D.F.,Wang, D.C. (登録日: 2011-05-04, 公開日: 2011-10-12, 最終更新日: 2023-11-01)

主引用文献

Bian, C.F.,Zhang, Y.,Sun, H.,Li, D.F.,Wang, D.C.
Structural basis for distinct binding properties of the human galectins to thomsen-friedenreich antigen
Plos One, 6:e25007-e25007, 2011

PubMed Abstract: The Thomsen-Friedenreich (TF or T) antigen, Galβ1-3GalNAcα1-O-Ser/Thr, is the core 1 structure of O-linked mucin type glycans appearing in tumor-associated glycosylation. The TF antigen occurs in about 90% of human cancer cells and is a potential ligand for the human endogenous galectins. It has been reported that human galectin-1 (Gal-1) and galectin-3 (Gal-3) can perform their cancer-related functions via specifically recognizing TF antigen. However, the detailed binding properties have not been clarified and structurally characterized. In this work, first we identified the distinct TF-binding abilities of Gal-1 and Gal-3. The affinity to TF antigen for Gal-3 is two orders of magnitude higher than that for Gal-1. The structures of Gal-3 carbohydrate recognition domain (CRD) complexed with TF antigen and derivatives, TFN and GM1, were then determined. These structures show a unique Glu-water-Arg-water motif-based mode as previously observed in the mushroom galectin AAL. The observation demonstrates that this recognition mode is commonly adopted by TF-binding galectins, either as endogenous or exogenous ones. The detailed structural comparisons between Gal-1 and Gal-3 CRD and mutagenesis experiments reveal that a pentad residue motif ((51)AHGDA(55)) at the loop (g1-L4) connecting β-strands 4 and 5 of Gal-1 produces a serious steric hindrance for TF binding. This motif is the main structural basis for Gal-1 with the low affinity to TF antigen. These findings provide the intrinsic structural elements for regulating the TF-binding activity of Gal-1 in some special conditions and also show certain target and approach for mediating some tumor-related bioactivities of human galectins.

PubMed: 21949831
DOI: 10.1371/journal.pone.0025007

実験手法

X-RAY DIFFRACTION (2 Å)