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Biological and physicochemical evaluation of the conformational stability of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)

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Abstract

Tumor necrosis factor (TNF)-related, apoptosis-inducing ligand (Apo2L/TRAIL) has a unique homotrimeric structure, and its conformational stability is essential for its apoptotic activity. The conformational stability of a modified version of TRAIL(114–281) with two additional domains of histidine tag and isoleucine zipper [His-ILZ-TRAIL(114–281)] was evaluated in various pH environments according to three different biological or physicochemical considerations: cytotoxicity, antibody-binding affinity, and tertiary structure. The biological properties of His-ILZ-TRAIL(114–281) were the most stably maintained at pH 6.0. The physicochemical analyses (circular dichroism and fluorescence spectroscopy) demonstrate that its bioactivity loss by pH challenge was originated from its structural collapse as a homotrimer.

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Acknowledgement

This work was supported by a grant from the Ministry of Science and Technology, Korea (M10414030001-05N1403-00140).

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Correspondence to Kang Choon Lee.

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Youn, Y.S., Shin, M.J., Chae, S.Y. et al. Biological and physicochemical evaluation of the conformational stability of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Biotechnol Lett 29, 713–721 (2007). https://doi.org/10.1007/s10529-006-9300-7

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  • DOI: https://doi.org/10.1007/s10529-006-9300-7

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