4LBO

Crystal structure of Human galectin-3 CRD in complex with a-GM3

Summary for 4LBO

• Entry DOI: 10.2210/pdb4lbo/pdb
• Related: 4LBJ 4LBK 4LBL 4LBM 4LBN
• Descriptor: Galectin-3, N-acetyl-alpha-neuraminic acid-(2-3)-beta-D-galactopyranose-(1-4)-beta-D-glucopyranose, CHLORIDE ION, ... (4 entities in total)
• Functional Keywords: galectin, carbohydrate-recognition, gm3, glycosphingolipid, beta sandwich, carbohydrate binding protein, sugar binding protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 16440.96

Authors

Collins, P.M.,Blanchard, H. (deposition date: 2013-06-20, release date: 2014-01-22, Last modification date: 2023-09-20)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.65 Å)