4LBJ

Crystal structure of Human galectin-3 CRD K176L mutant in complex with LNT

4LBJ の概要

• エントリーDOI: 10.2210/pdb4lbj/pdb
• 関連するPDBエントリー: 4LBK 4LBL 4LBM 4LBN 4LBO
• 分子名称: Galectin-3, beta-D-galactopyranose-(1-3)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-3)-beta-D-galactopyranose-(1-4)-beta-D-glucopyranose, CHLORIDE ION, ... (4 entities in total)
• 機能のキーワード: galectin, carbohydrate-recognition, lnt, glycosphingolipid, beta sandwich, carbohydrate binding protein, sugar binding protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 16462.19

構造登録者

Bum-Erdene, K.,Blanchard, H. (登録日: 2013-06-20, 公開日: 2014-01-22, 最終更新日: 2023-09-20)

主引用文献

Collins, P.M.,Bum-Erdene, K.,Yu, X.,Blanchard, H.
Galectin-3 interactions with glycosphingolipids.
J.Mol.Biol., 426:1439-1451, 2014

PubMed Abstract: Galectins have essential roles in pathological states including cancer, inflammation, angiogenesis and microbial infections. Endogenous receptors include members of the lacto- and neolacto-series glycosphingolipids present on mammalian cells and contain the tetrasaccharides lacto-N-tetraose (LNT) and lacto-N-neotetraose (LNnT) that form their core structural components and also ganglio-series glycosphingolipids. We present crystallographic structures of the carbohydrate recognition domain of human galectin-3, both wild type and a mutant (K176L) that influenced ligand affinity, in complex with LNT, LNnT and acetamido ganglioside a-GM3 (α2,3-sialyllactose). Key structural features revealed include galectin-3's demonstration of a binding mode towards gangliosides distinct from that to the lacto/neolacto-glycosphingolipids, with its capacity for recognising the core β-galactoside region being challenged when the core oligosaccharide epitope of ganglio-series glycosphingolipids (GM3) is embedded within particular higher-molecular-weight glycans. The lacto- and neolacto- glycosphingolipids revealed different orientations of their terminal galactose in the galectin-3-bound LNT and LNnT structures that has significant ramifications for the capacity of galectin-3 to interact with higher-order lacto/neolacto-series glycosphingolipids such as ABH blood group antigens and the HNK-1 antigen that is common on leukocytes. LNnT also presents an important model for poly-N-acetyllactosamine-containing glycans and provides insight into galectin-3's accommodation of extended oligosaccharides such as the poly-N-acetyllactosamine-modified N- and O-glycans that, via galectin-3 interaction, facilitate progression of lung and bladder cancers, respectively. These findings provide the first atomic detail of galectin-3's interactions with the core structures of mammalian glycosphingolipids, providing information important in understanding the capacity of galectin-3 to engage with receptors identified as facilitators of major disease.

PubMed: 24326249
DOI: 10.1016/j.jmb.2013.12.004

実験手法

X-RAY DIFFRACTION (1.8 Å)