The regulatory mechanism of the caspase 6 pro-domain revealed by crystal   structure and biochemical assays

doi:10.1107/S1399004713024218

CORC > 北京大学 > 生命科学学院

	The regulatory mechanism of the caspase 6 pro-domain revealed by crystal structure and biochemical assays
	Cao, Qin ; Wang, Xiao-Jun ; Li, Lan-Fen ; Su, Xiao-Dong
刊名	acta crystallographica section d biological crystallography
	2014
关键词	MUTANT HUNTINGTIN SELF-ACTIVATION AMINO-ACID IN-VIVO CLEAVAGE DEGENERATION CONFORMATION METHIONINE PROTEINS CASCADE
DOI	10.1107/S1399004713024218
英文摘要	Caspase 6 (CASP6) is a neuron degeneration-related protease and is widely considered to be a potential drug-design target against neurodegenerative diseases such as Huntington's disease and Alzheimer's disease. The N-terminal pro-peptide of CASP6, also referred to as the pro-domain, contains 23 residues and its functional role remains elusive. In this study, the crystal structure of a full-length CASP6 zymogen mutant, proCASP6H121A, was solved. Although the pro-domain was flexible in the crystal, without visible electron density, structural analyses combined with biochemical assays revealed that the pro-domain inhibited CASP6 auto-activation by inhibiting intramolecular cleavage at the intersubunit cleavage site TEVD 193 and also by preventing this site from intermolecular cleavage at low protein concentration through a so-called 'suicide-protection' mechanism. Further experiments showed that the length of the pro-domain and the side chain of Asn18 played critical roles in suicide protection. These results disclosed a new inhibitory mechanism of CASP6 and shed light on the pathogenesis and therapeutically relevant study of CASP6-related neurodegenerative diseases.; Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography; SCI(E); PubMed; 2; ARTICLE; xdsu@pku.edu.cn; Pt 1; 58-67; 70
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/342454]
专题	生命科学学院
推荐引用方式 GB/T 7714	Cao, Qin,Wang, Xiao-Jun,Li, Lan-Fen,et al. The regulatory mechanism of the caspase 6 pro-domain revealed by crystal structure and biochemical assays[J]. acta crystallographica section d biological crystallography,2014.
APA	Cao, Qin,Wang, Xiao-Jun,Li, Lan-Fen,&Su, Xiao-Dong.(2014).The regulatory mechanism of the caspase 6 pro-domain revealed by crystal structure and biochemical assays.acta crystallographica section d biological crystallography.
MLA	Cao, Qin,et al."The regulatory mechanism of the caspase 6 pro-domain revealed by crystal structure and biochemical assays".acta crystallographica section d biological crystallography (2014).