Solution structure of c-FLIP death effector domains

Zhi-Qiang Bai; Xiaofang Ma; Bin Liu; Tao Huang; Kaifeng Hu

doi:10.1016/j.bbrc.2022.05.086

Solution structure of c-FLIP death effector domains

Biochem Biophys Res Commun. 2022 Aug 30;617(Pt 2):1-6. doi: 10.1016/j.bbrc.2022.05.086. Epub 2022 May 29.

Authors

Zhi-Qiang Bai¹, Xiaofang Ma², Bin Liu³, Tao Huang³, Kaifeng Hu⁴

Affiliations

¹ State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, 132 Lanhei Road, Heilongtan, Kunming, 650201, Yunnan, China; Innovative Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China; University of Chinese Academy of Sciences, Beijing, 100049, China.
² Innovative Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China.
³ State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, 132 Lanhei Road, Heilongtan, Kunming, 650201, Yunnan, China; University of Chinese Academy of Sciences, Beijing, 100049, China.
⁴ State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, 132 Lanhei Road, Heilongtan, Kunming, 650201, Yunnan, China; Innovative Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China. Electronic address: kaifenghu@cdutcm.edu.cn.

PMID: 35688044
DOI: 10.1016/j.bbrc.2022.05.086

Abstract

The formation of death-inducing signaling complex (DISC) and death effector domain (DED) filament initiates extrinsic apoptosis. Recruitment and activation of procaspase-8 at the DISC are regulated by c-FLIP. The interaction between c-FLIP and procaspase-8 is mediated by their tandem DEDs (tDED). However, the structure of c-FLIP^tDED and how c-FLIP interferes with procaspase-8 activation at the DISC remain elusive. Here, we solved the monomeric structure of c-FLIP^tDED (F114G) at near physiological pH by solution nuclear magnetic resonance (NMR). Structural superimposition reveals c-FLIP^tDED (F114G) adopts a structural topology similar to that of procaspase-8^tDED. Our results provide a structural basis for understanding how c-FLIP interacts with procaspase-8 and the molecular mechanisms of c-FLIP in regulating cell death.

Keywords: Anti-apoptosis; Death effector domains; c-FLIP.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Apoptosis
CASP8 and FADD-Like Apoptosis Regulating Protein* / metabolism
Caspase 8 / metabolism
Death Effector Domain*
Signal Transduction

Substances

CASP8 and FADD-Like Apoptosis Regulating Protein
Caspase 8