Molecular basis of dimerization of initiator caspase was revealed by crystal structure of caspase-8 pro-domain

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Abstract

The assembly of death-inducing signaling complex (DISC) for activation of initiator caspase is a key step for the receptor-mediated apoptosis signaling. Many death effector domain (DED)-containing proteins are involved in DISC assembly and controlling. One of the main DISC component, caspase-8, contains DED and DED-mediated dimerization and oligomerization in the DISC is critical for the activation of this initiator caspase. There have been intensive studies to understand DED-mediated dimerization and oligomerization for the DISC assembly but no clear answer has been provided and there are many controversial arguments. Here, we suggested novel dimerization process of tandem DED of caspase-8 with crystallographic study.

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Acknowledgements

I thank the staff at BL-5C of the Pohang Accelerator Laboratory (Pohang, Korea) for their kind help with data collection. This study was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (NRF-2017M3A9D8062960, NRF-2018R1A2B2003635, and NRF-2018R1A4A1023822) and a grant from the Korea Healthcare Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (HI17C0155).

Author contributions

HHP designed the project, performed experiments, and wrote the manuscript.

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Correspondence to Hyun Ho Park.

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The author declares that he has no conflict of interest.

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Edited by V. Dixit

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