2013
DOI: 10.1074/jbc.m113.480467
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Recognition of the Thomsen-Friedenreich Pancarcinoma Carbohydrate Antigen by a Lamprey Variable Lymphocyte Receptor

Abstract: Background: Variable lymphocyte receptors (VLRs) bind tumor-associated carbohydrates, such as Thomsen-Friedenreich antigen (TF␣), with high selectivity. Results:The crystal structure of a VLR-TF␣ complex coupled with thermodynamic analysis revealed the basis for selectivity. Conclusion: VLRs utilize leucine-rich repeats to recognize glycans with affinity comparable to that of lectins and antibodies. Significance: The VLR-TF␣ structure provides a template for engineering VLRs to bind biomedically relevant glyca… Show more

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Cited by 39 publications
(61 citation statements)
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References 36 publications
(62 reference statements)
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“…Similar carbohydrate recognition through tryptophan residues was seen by Luo et al in recognition of Thomsen-Friedenreich antigen by a VLR protein. 18 Although our observed affinities are an order of magnitude lower than reported for the full-length NOD2 protein 55 it is important to note that CLRR2 is representative of the entire NOD family and shares only 70% sequence identity with NOD2.…”
Section: Chemical Denaturationmentioning
confidence: 53%
See 1 more Smart Citation
“…Similar carbohydrate recognition through tryptophan residues was seen by Luo et al in recognition of Thomsen-Friedenreich antigen by a VLR protein. 18 Although our observed affinities are an order of magnitude lower than reported for the full-length NOD2 protein 55 it is important to note that CLRR2 is representative of the entire NOD family and shares only 70% sequence identity with NOD2.…”
Section: Chemical Denaturationmentioning
confidence: 53%
“…43 The sequence identities for the NOD and NLRP-b consensus sequences are 57%; however, the overall conservation in most positions in the NLRP-b sequence exceeds the NOD. For example, positions 6,13,18,19,21,22,25,26, and 27 in the NLRP-b MSA all have significantly higher conservation than the NOD sequence [ Fig. 1(b)].…”
Section: Consensus Sequence Of Nod Subgroupmentioning
confidence: 99%
“…3B). This insert, whose secondary structure also varies, is critical for recognition of protein and carbohydrate antigens (14,15,(22)(23)(24)(25). The average length of the LRRCT insert in VLRCs (2 residues) is much less than in VLRAs (10 residues) or VLRBs (8 residues), and sequence variation in the LRRCT module of VLRCs is substantially lower than in LRRCT of the other two VLR types (19,29).…”
Section: Resultsmentioning
confidence: 99%
“…Several carbohydrate-binding lectins and mammalian antibodies have been investigated for specific binding to glycosylated proteins; however, these binders generally suffer from low affinity and broad specificity, thus limiting their clinical utility [39][40][41][42]. Variable lymphocyte receptors (VLRs), which are LRRs involved in the adaptive immunity of jawless vertebrates, have been successfully engineered for recognition of several glycosylated proteins [12,43,44]. For example, Hong et al [33] describe a yeast surface display screen of VLRs from lamprey that enabled the selection of binders for a number of glycan targets with nanomolar affinities.…”
Section: Other Biomolecular Targetsmentioning
confidence: 99%
“…Designed ankyrin repeat proteins (DARPins), tetratricopeptide repeats (TPRs), armadillo repeat proteins (ARMs) and leucine rich repeat proteins (LRRs) have all been used for development of high-affinity binders [9][10][11][12][13]. For this reason, designed repeat proteins that have been successfully used for imaging and/or biosensing applications will remain the focus of this review.…”
mentioning
confidence: 99%