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Flexible loop and helix 2 domains of TCTP are the functional domains of dimerized TCTP

Title
Flexible loop and helix 2 domains of TCTP are the functional domains of dimerized TCTP
Authors
Lee H.Kim M.-S.Lee J.-S.Cho H.Park J.Hae Shin D.Lee K.
Ewha Authors
이경림신동해
SCOPUS Author ID
이경림scopus; 신동해scopus
Issue Date
2020
Journal Title
Scientific Reports
ISSN
2045-2322JCR Link
Citation
Scientific Reports vol. 10, no. 1
Publisher
Nature Research
Indexed
SCI; SCIE; SCOPUS WOS scopus
Document Type
Article
Abstract
Translationally controlled tumor protein (TCTP), also called histamine releasing factor, is an evolutionarily conserved multifunctional protein in eukaryotes. We previously reported that extracellular TCTP acquires its cytokine-like function following dimerization. This study aims to identify the functional domain involved in the cytokine-like function of dimerized TCTP (dTCTP). We performed X-ray crystallographic studies and a deletion mutant of dTCTP which lacks the flexible loop domain. Synthetic peptides corresponding to TCTP domains and antibodies developed against them were examined for the anti-allergic effect. In an OVA-induced airway inflammation mouse model, inhibitory effect of synthetic peptides was evaluated. dTCTP was mediated by dimers between Cys172s of TCTP monomers. Synthetic peptides corresponding to the flexible loop and helix 2 domain of TCTP, and antibodies against them inhibited dTCTP-induced IL-8 release. In particular, the TCTP mutant lacking the flexible loop domain decreased the inflammatory cytokine activity of dTCTP. We conclude that the flexible loop and helix 2 domain of TCTP are the functional domains of dTCTP. They may have the potential to be therapeutic targets in the suppression of allergic reactions induced by dTCTP. © 2020, The Author(s).
DOI
10.1038/s41598-019-57064-9
Appears in Collections:
약학대학 > 약학과 > Journal papers
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