Structural Insights into VLR Fine Specificity for Blood Group Carbohydrates

被引:35
作者
Collins, Bernard C. [1 ,2 ]
Gunn, Robin J. [1 ,2 ]
McKitrick, Tanya R. [3 ]
Cummings, Richard D. [3 ]
Cooper, Max D. [4 ,5 ]
Herrin, Brantley R. [4 ,5 ]
Wilson, Ian A. [1 ,2 ]
机构
[1] Scripps Res Inst, Dept Integrat Struct & Computat Biol, La Jolla, CA 92037 USA
[2] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA
[3] Harvard Med Sch, Natl Ctr Funct Glyc, Beth Israel Deaconess Med Ctr, Dept Surg, 330 Brookline Ave, Boston, MA 02215 USA
[4] Emory Univ, Emory Vaccine Ctr, 1462 Clifton Rd North East, Atlanta, GA 30322 USA
[5] Emory Univ, Dept Pathol & Lab Med, 1462 Clifton Rd North East, Atlanta, GA 30322 USA
关键词
VARIABLE LYMPHOCYTE RECEPTORS; IMMUNE-RESPONSE; LECTIN-I; RECOGNITION; BINDING; EVOLUTION; AFFINITY; ANTIGEN; ANTIBODIES; SELECTION;
D O I
10.1016/j.str.2017.09.003
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:1667 / +
页数:16
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