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

Heewon Lee, Mi Sun Kim, Ji Sun Lee, Hyunsoo Cho, Jimin Park, Dong Hae Shin, Kyunglim Lee

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11 Scopus citations


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.

Original languageEnglish
Article number197
JournalScientific Reports
Issue number1
StatePublished - 1 Dec 2020

Bibliographical note

Funding Information:
We sincerely thank Drs. Miyoung Kim and Moonhee Kim for fruitful discussions and help with in vitro assays. This research was supported by Basic Science Research Program (2017R1A2B2004023) and Bio & Medical Technology Development Program (2018M3A9A8021689) through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and future Planning and by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI17C0631).

Publisher Copyright:
© 2020, The Author(s).


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