The Legionella HtrA homologue DegQ is a self-compartmentizing protease that forms large 12-meric assemblies
文献类型：期刊论文
| 作者 | Wrase, Robert3; Scott, Hannah3; Hilgenfeld, Rolf1,2,3; Hansen, Guido3 |
| 刊名 | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
 |
| 出版日期 | 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. |
| WOS关键词 | ESCHERICHIA-COLI DEGP ; QUALITY-CONTROL ; CHAPERONE FUNCTION ; CRYSTAL-STRUCTURE ; STRESS-SENSOR ; ACTIVATION ; MECHANISM ; PROTEINS ; CLEAVAGE ; BINDING |
| 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研究方向 | Science & Technology - Other Topics |
| 语种 | 英语 |
| WOS记录号 | WOS:000292251000029 |
| 出版者 | NATL ACAD SCIENCES |
| 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. |
入库方式： OAI收割
来源：上海药物研究所
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