5UF4

Crystal Structure of Variable Lymphocyte Receptor (VLR) O13 with LNnT bound

Summary for 5UF4

• Entry DOI: 10.2210/pdb5uf4/pdb
• Related: 5UEI 5UF1 5UFB 5UFC 5UFD 5UFF
• Descriptor: O13, beta-D-galactopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-3)-beta-D-galactopyranose-(1-4)-alpha-D-glucopyranose (3 entities in total)
• Functional Keywords: variable lymphocyte receptors, vlr, leucine-rich repeat, lrr, adaptive immunity, immune system, sea lamprey, jawless fish, receptor, glycan binding, glycan receptor
• Biological source: Petromyzon marinus (Sea lamprey)
• Total number of polymer chains: 3
• Total formula weight: 84458.86

Authors

Gunn, R.J.,Collins, B.C.,McKitrick, T.R.,Cummings, R.D.,Cooper, M.D.,Herrin, B.R.,Wilson, I.A. (deposition date: 2017-01-03, release date: 2017-10-18, Last modification date: 2024-10-16)

Primary citation

Collins, B.C.,Gunn, R.J.,McKitrick, T.R.,Cummings, R.D.,Cooper, M.D.,Herrin, B.R.,Wilson, I.A.
Structural Insights into VLR Fine Specificity for Blood Group Carbohydrates.
Structure, 25:1667-1678.e4, 2017

PubMed 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.

PubMed: 28988747
DOI: 10.1016/j.str.2017.09.003

Experimental method

X-RAY DIFFRACTION (2.04 Å)