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http://dx.doi.org/10.5762/KAIS.2019.20.9.211

Key Structural Features of PigCD45RO as an Essential Regulator of T-cell Antigen Receptor Signaling  

Chai, Han-Ha (Animal Genomics and Bioinformatics Division, National Institute of Animal Science and Collage of Pharmacy, Chonnam National University)
Lim, Dajeong (Animal Genomics and Bioinformatics Division, National Institute of Animal Science)
Publication Information
Journal of the Korea Academia-Industrial cooperation Society / v.20, no.9, 2019 , pp. 211-226 More about this Journal
Abstract
Pig CD45, the leukocyte common antigen, is encoded by the PTPRC gene and CD45 is a T cell-type specific tyrosine phosphatase with alternative splicing of its exons. The CD45 is a coordinated regulator of T cell antigen receptor (TCR) signal transduction achieved by dephosphorylating the phosphotyrosine of its substances, including $CD3{\zeta}$ chain of TCR, Lck, Fyn, and Zap-70 kinase. A dysregulation of CD45 is associated with a multitude of immune disease and has been a target for immuno-drug discovery. To characterize its key structural features with the effects of regulating TCR signaling, this study predicted the unknown structure of pig CD45RO (the smallest isoform) and the complex structure bound to the ITAM (REEpYDV) of $CD3{\zeta}$ chain via homology modeling and docking the peptide, based on the known human CD45 structures. These features were integrated into the structural plasticity of extracellular domains and functional KNRY and PTP signature motifs (the role of a narrow entrance into ITAM binding site) of the tyrosine phosphatase domains in a cytoplasmic region from pig CD45RO. This contributes to the selective recognition of phosphotyrosine from its substrates by adjusting the structural stability and binding affinity of the complex. The characterized features of pigCD45RO can be applied in virtual screening of the T-cell specific immunomodulator.
Keywords
CD45RO; Tyrosine Phosphatase; T-cell Antigen Receptor; Signaling Transduction; Regulator;
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