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Structural Insights into VLR Fine Specificity for Blood Group Carbohydrates.

ABSTRACT: High-quality reagents to study and detect glycans with high specificity for research and clinical applications are severely lacking. Here, we structurally and functionally characterize several variable lymphocyte receptor (VLR)-based antibodies from lampreys immunized with O erythrocytes that specifically recognize the blood group H-trisaccharide type II antigen. Glycan microarray analysis and biophysical data reveal that these VLRs exhibit greater specificity for H-trisaccharide compared with the plant lectin UEA-1, which is widely used in blood typing. Among these antibodies, O13 exhibits superior specificity for H-trisaccharide, the basis for which is revealed by comparative analysis of high-resolution VLR:glycan crystal structures. Using a structure-guided approach, we designed an O13 mutant with further enhanced specificity for H-trisaccharide. These insights into glycan recognition by VLRs suggest that lampreys can produce highly specific glycan antibodies, and are a valuable resource for the production of next-generation glycan reagents for biological and biomedical research and as diagnostics and therapeutics.

SUBMITTER: Collins BC

PROVIDER: S-EPMC5677568 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Structural Insights into VLR Fine Specificity for Blood Group Carbohydrates.

Collins Bernard C BC Gunn Robin J RJ McKitrick Tanya R TR Cummings Richard D RD Cooper Max D MD Herrin Brantley R BR Wilson Ian A IA

Structure (London, England : 1993) 20171005 11

High-quality reagents to study and detect glycans with high specificity for research and clinical applications are severely lacking. Here, we structurally and functionally characterize several variable lymphocyte receptor (VLR)-based antibodies from lampreys immunized with O erythrocytes that specifically recognize the blood group H-trisaccharide type II antigen. Glycan microarray analysis and biophysical data reveal that these VLRs exhibit greater specificity for H-trisaccharide compared with t ...[more]

PMID: 28988747

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Structural Insights into VLR Fine Specificity for Blood Group Carbohydrates.

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Structural Insights into VLR Fine Specificity for Blood Group Carbohydrates.

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