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Publication Abstract from PubMed

Variable lymphocyte receptors (VLRs) are leucine-rich repeat (LRR) proteins that mediate adaptive immunity in jawless vertebrates. VLRs were recently shown to recognize glycans, such as the tumor-associated Thomsen-Friedenreich antigen (TFalpha; Galbeta1-3GalNAcalpha), with a selectivity rivaling or exceeding that of lectins and antibodies. To understand the basis for TFalpha recognition by one such VLR (VLRB.aGPA.23), we measured thermodynamic parameters for the binding interaction, and determined the structure of the VLRB.aGPA.23-TFalpha complex to 2.2 A resolution. In the structure, four tryptophan residues form a tight hydrophobic cage encasing the TFalpha disaccharide that completely excludes buried water molecules. This cage, together with hydrogen bonding of sugar hydroxyls to polar side chains, explains the high selectivity of VLRB.aGPA.23. The topology of the glycan-binding site of VLRB.aGPA.23 differs markedly from those of lectins or antibodies, which typically consist of long, convex grooves for accommodating the oligosaccharide. Instead, the TFalpha disaccharide is sandwiched between a variable loop and the concave surface of the VLR formed by the beta-strands of the LRR modules. Longer oligosaccharides are predicted to extend perpendicularly across the beta-strands, requiring them to bend to match the concavity of the VLR solenoid.

Recognition of the Thomsen-Friedenreich pancarcinoma carbohydrate antigen by a lamprey variable lymphocyte receptor.,Luo M, Velikovsky CA, Yang X, Siddiqui MA, Hong X, Barchi JJ, Gildersleeve JC, Pancer Z, Mariuzza RA J Biol Chem. 2013 Jun 19. PMID:23782692^[1]

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