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Publication Abstract from PubMed

Mannose-binding type Jacalin-related lectins (mJRLs) bind to branched N-glycans via conserved sugar binding sites. Despite significant 3D structural similarities, each mJRL is known to have a unique binding preference towards various N-glycans. However, the molecular basis of varying binding preference is substantially unknown. Here we report a detailed comparison of N-glycan binding preference for two mJRLs, Orysata and Calsepa using frontal affinity chromatography (FAC), X-ray and molecular modeling. The FAC analysis using a panel of N-glycans shows difference in N-glycan binding preference between the lectins. Orysata shows broader specificity toward most high-mannose-type glycans as well as biantennary complex-type glycans bearing an extension on the Manalpha1-6 branch. Whereas, Calsepa shows narrow specificity to complex-type glycans with bisecting GlcNAc. The X-ray crystallographic structure reveals that two Orysata lectins bind to one biantennary N-glycan (2:1 binding) where one lectin binds to mannose of the alpha1-3 branch, while the other interacts with an N-acetylglucosamine of the alpha1-6 branch. In contrast, Calsepa shows 1:1 binding where alpha1-3 branch and core chitobiose region N-glycan interacts with lectin, while alpha1-6 branch is flipped back to the chitobiose core. Molecular dynamics study of Orysata bound to N-glycans substantiate possibility of two binding modes for each N-glycan. Binding free energies calculated separately for alpha1-3 and alpha1-6 branches of each N-glycan suggest both branches can bind to Orysata. Overall these results suggest that each branch of N-glycan has a distinct role in binding mJRLs and the non-binding branch can contribute significantly to the binding affinity and hence to the specificity.

Distinct roles for each N-glycan branch interacting with mannose-binding type Jacalin-related lectins Orysata and Calsepa.,Nagae M, Mishra SK, Hanashima S, Tateno H, Yamaguchi Y Glycobiology. 2017 Sep 7. doi: 10.1093/glycob/cwx081. PMID:28973127^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.