The Legionella HtrA homologue DegQ is a self-compartmentizing protease that forms large 12-meric assemblies

doi:10.1073/pnas.1101084108

	The Legionella HtrA homologue DegQ is a self-compartmentizing protease that forms large 12-meric assemblies
	Wrase, Robert 3; Scott, Hannah 3; Hilgenfeld, Rolf 1,2,3; Hansen, Guido 3
刊名	PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
	2011-06-28
卷号	108 期号:26 页码:10490-10495
关键词	X-ray crystallography protein quality control oligomerization PDZ domain molecular switch
ISSN号	0027-8424
DOI	10.1073/pnas.1101084108
文献子类	Article
英文摘要	Proteases of the HtrA family are key factors dealing with folding stress in the periplasmatic compartment of prokaryotes. In Escherichia coli, the well-characterized HtrA family members DegS and DegP counteract the accumulation of unfolded outer-membrane proteins under stress conditions. Whereas DegS serves as a folding-stress sensor, DegP is a chaperone-protease facilitating refolding or degradation of defective outer-membrane proteins. Here, we report the 2.15-angstrom-resolution crystal structure of the second major chaperone-protease of the periplasm, DegQ from Legionella fallonii. DegQ assembles into large, cage-like 12-mers that form independently of unfolded substrate proteins. We provide evidence that 12-mer formation is essential for the degradation of substrate proteins but not for the chaperone activity of DegQ. In the current model for the regulation of periplasmatic chaper-one-proteases, 6-meric assemblies represent important protease-resting states. However, DegQ is unable to form such 6-mers, suggesting divergent regulatory mechanisms for DegQ and DegP. To understand how the protease activity of DegQ is controlled, we probed its functional properties employing designed protein variants. Combining crystallographic, biochemical, and mutagenic data, we present a mechanistic model that suggests how protease activity of DegQ 12-mers is intrinsically regulated and how deleterious proteolysis by free DegQ 3-mers is prevented. Our study sheds light on a previously uncharacterized component of the prokaryotic stress-response system with implications for other members of the HtrA family.
资助项目	Helmholtz Zentrum Berlin fur Materialien und Energie[00000000] ; Freie Universitat Berlin[00000000] ; Humboldt-Universitat zu Berlin[00000000] ; Max-Delbruck Centrum[00000000] ; Leibniz-Institut fur Molekulare Pharmakologie[00000000] ; European Commission (EC)[R II 3-CT-2004-506008] ; European Commission (EC)[LSH-2005-037793] ; Deutsche Forschungsgemeinschaft Cluster of Excellence[EXC 306] ; Fonds der Chemischen Industrie[00000000] ; Chinese Academy of Sciences[2010T1S6]
WOS关键词	ESCHERICHIA-COLI DEGP ; QUALITY-CONTROL ; CHAPERONE FUNCTION ; CRYSTAL-STRUCTURE ; STRESS-SENSOR ; ACTIVATION ; MECHANISM ; PROTEINS ; CLEAVAGE ; BINDING
WOS研究方向	Science & Technology - Other Topics
语种	英语
出版者	NATL ACAD SCIENCES
WOS记录号	WOS:000292251000029
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/278494]
专题	中国科学院上海药物研究所
通讯作者	Hilgenfeld, Rolf
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 2.DESY, Lab Struct Biol Infect & Inflammat, D-22603 Hamburg, Germany; 3.Univ Lubeck, Ctr Struct & Cell Biol Med, Inst Biochem, D-23538 Lubeck, Germany;
推荐引用方式 GB/T 7714	Wrase, Robert,Scott, Hannah,Hilgenfeld, Rolf,et al. The Legionella HtrA homologue DegQ is a self-compartmentizing protease that forms large 12-meric assemblies[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2011,108(26):10490-10495.
APA	Wrase, Robert,Scott, Hannah,Hilgenfeld, Rolf,&Hansen, Guido.(2011).The Legionella HtrA homologue DegQ is a self-compartmentizing protease that forms large 12-meric assemblies.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,108(26),10490-10495.
MLA	Wrase, Robert,et al."The Legionella HtrA homologue DegQ is a self-compartmentizing protease that forms large 12-meric assemblies".PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 108.26(2011):10490-10495.