2R0F

Ligand free structure of fungal lectin CGL3

Summary for 2R0F

• Entry DOI: 10.2210/pdb2r0f/pdb
• Related: 1UL9 1ULC 1ULD 1ULE 1ULF 1ULG
• Descriptor: CGL3 lectin (2 entities in total)
• Functional Keywords: galectin-related, lectin, sugar binding protein, chitooligosaccharides
• Biological source: Coprinus cinereus (Inky cap fungus)
• Cellular location: Secreted, extracellular space, extracellular matrix (By similarity): Q206Z5
• Total number of polymer chains: 2
• Total formula weight: 37516.52

Authors

Waelti, M.A.,Walser, P.J.,Thore, S.,Gruenler, A.,Ban, N.,Kuenzler, M.,Aebi, M. (deposition date: 2007-08-19, release date: 2008-05-20, Last modification date: 2023-10-25)

Primary citation

Waelti, M.A.,Walser, P.J.,Thore, S.,Gruenler, A.,Bednar, M.,Kuenzler, M.,Aebi, M.
Structural Basis for Chitotetraose Coordination by CGL3, a Novel Galectin-Related Protein from Coprinopsis cinerea
J.Mol.Biol., 379:146-159, 2008

PubMed Abstract: Recent advances in genome sequencing efforts have revealed an abundance of novel putative lectins. Among these, many galectin-related proteins, characterized by many conserved residues but intriguingly lacking critical amino acids, have been found in all corners of the eukaryotic superkingdom. Here we present a structural and biochemical analysis of one representative, the galectin-related lectin CGL3 found in the inky cap mushroom Coprinopsis cinerea. This protein contains all but one conserved residues known to be involved in beta-galactoside binding in galectins. A Trp residue strictly conserved among galectins is changed to an Arg in CGL3 (R81). Accordingly, the galectin-related protein is not able to bind lactose. Screening of a glycan array revealed that CGL3 displays preference for oligomers of beta1-4-linked N-acetyl-glucosamines (chitooligosaccharides) and GalNAc beta 1-4GlcNAc (LacdiNAc). Carbohydrate-binding affinity of this novel lectin was quantified using isothermal titration calorimetry, and its mode of chitooligosaccharide coordination not involving any aromatic amino acid residues was studied by X-ray crystallography. Structural information was used to alter the carbohydrate-binding specificity and substrate affinity of CGL3. The importance of residue R81 in determining the carbohydrate-binding specificity was demonstrated by replacing this Arg with a Trp residue (R81W). This single-amino-acid change led to a lectin that failed to bind chitooligosaccharides but gained lactose binding. Our results demonstrate that, similar to the legume lectin fold, the galectin fold represents a conserved structural framework upon which dramatically altered specificities can be grafted by few alterations in the binding site and that, in consequence, many metazoan galectin-related proteins may represent lectins with novel carbohydrate-binding specificities.

PubMed: 18440554
DOI: 10.1016/j.jmb.2008.03.062

Experimental method

X-RAY DIFFRACTION (2 Å)