Crystal structure of the death effector domains of caspase-8.

Abstract

Caspase-8 is a key mediator in various biological processes such as apoptosis, necroptosis, inflammation, T/B cells activation, and cell motility. Caspase-8 is characterized by the N-terminal tandem death effector domains (DEDs) and the C-terminal catalytic protease domain. The DEDs mediate diverse functions of caspase-8 through homotypic interactions of the DEDs between caspase-8 and its partner proteins. Here, we report the first crystal structure of the DEDs of caspase-8. The overall structure of the DEDs of caspase-8 is similar to that of the DEDs of vFLIP MC159, which is composed of two tandem death effector domains that closely associate with each other in a head-to-tail manner. Structural analysis reveals distinct differences in the region connecting helices α2b and α4b in the second DED of the DEDs between caspase-8 and MC159, in which the helix α3b in MC159 is replaced by a loop in caspase-8. Moreover, the different amino acids in this region might confer the distinct features of solubility and aggregation for the DEDs of caspase-8 and MC159.

• Authors: Chen Shen, Hong Yue, Jianwen Pei, Xiaomin Guo, Tao Wang, Jun-Min Quan
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 463 Issue 3 Pg. 297-302 (Jul 31 2015) ISSN: 1090-2104 [Electronic] United States
• PMID: 26003730 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Viral Proteins
• viral FLIP protein, Molluscum contagiosum virus
• Caspase 8

Topics

• Amino Acid Sequence
• Caspase 8 (chemistry)
• Crystallography, X-Ray
• Humans
• Models, Molecular
• Molecular Sequence Data
• Molluscum Contagiosum (virology)
• Molluscum contagiosum virus (chemistry)
• Protein Structure, Tertiary
• Sequence Alignment
• Viral Proteins (chemistry)