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| | ==HtrA proteases are activated by a conserved mechanism that can be triggered by distinct molecular cues== | | ==HtrA proteases are activated by a conserved mechanism that can be triggered by distinct molecular cues== |
| - | <StructureSection load='3mh5' size='340' side='right' caption='[[3mh5]], [[Resolution|resolution]] 3.00Å' scene=''> | + | <StructureSection load='3mh5' size='340' side='right'caption='[[3mh5]], [[Resolution|resolution]] 3.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3mh5]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Ecoli Ecoli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3MH5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3MH5 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3mh5]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3MH5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3MH5 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DFP:DIISOPROPYL+PHOSPHONATE'>DFP</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3mh4|3mh4]], [[3mh6|3mh6]], [[3mh7|3mh7]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DFP:DIISOPROPYL+PHOSPHONATE'>DFP</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DegP ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83333 ECOLI])</td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3mh5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3mh5 OCA], [https://pdbe.org/3mh5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3mh5 RCSB], [https://www.ebi.ac.uk/pdbsum/3mh5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3mh5 ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3mh5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3mh5 OCA], [http://pdbe.org/3mh5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3mh5 RCSB], [http://www.ebi.ac.uk/pdbsum/3mh5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3mh5 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/DEGP_ECOLI DEGP_ECOLI]] DegP acts as a chaperone at low temperatures but switches to a peptidase (heat shock protein) at higher temperatures. It degrades transiently denatured and unfolded proteins which accumulate in the periplasm following heat shock or other stress conditions. DegP is efficient with Val-Xaa and Ile-Xaa peptide bonds, suggesting a preference for beta-branched side chain amino acids. Only unfolded proteins devoid of disulfide bonds appear capable of being cleaved, thereby preventing non-specific proteolysis of folded proteins. Its proteolytic activity is essential for the survival of cells at elevated temperatures. It can degrade IciA, ada, casein, globin and PapA. DegP shares specificity with DegQ. DegP is also involved in the biogenesis of partially folded outer-membrane proteins (OMP).<ref>PMID:2180903</ref> <ref>PMID:8830688</ref> <ref>PMID:10319814</ref> <ref>PMID:18505836</ref> <ref>PMID:12730160</ref> <ref>PMID:18496527</ref> | + | [https://www.uniprot.org/uniprot/DEGP_ECOLI DEGP_ECOLI] DegP acts as a chaperone at low temperatures but switches to a peptidase (heat shock protein) at higher temperatures. It degrades transiently denatured and unfolded proteins which accumulate in the periplasm following heat shock or other stress conditions. DegP is efficient with Val-Xaa and Ile-Xaa peptide bonds, suggesting a preference for beta-branched side chain amino acids. Only unfolded proteins devoid of disulfide bonds appear capable of being cleaved, thereby preventing non-specific proteolysis of folded proteins. Its proteolytic activity is essential for the survival of cells at elevated temperatures. It can degrade IciA, ada, casein, globin and PapA. DegP shares specificity with DegQ. DegP is also involved in the biogenesis of partially folded outer-membrane proteins (OMP).<ref>PMID:2180903</ref> <ref>PMID:8830688</ref> <ref>PMID:10319814</ref> <ref>PMID:18505836</ref> <ref>PMID:12730160</ref> <ref>PMID:18496527</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </div> | | </div> |
| | <div class="pdbe-citations 3mh5" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 3mh5" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Heat Shock Protein structures|Heat Shock Protein structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Ecoli]] | + | [[Category: Escherichia coli K-12]] |
| - | [[Category: Clausen, T]] | + | [[Category: Large Structures]] |
| - | [[Category: Huber, R]] | + | [[Category: Clausen T]] |
| - | [[Category: Krojer, T]] | + | [[Category: Huber R]] |
| - | [[Category: Sawa, J]] | + | [[Category: Krojer T]] |
| - | [[Category: Degp]]
| + | [[Category: Sawa J]] |
| - | [[Category: Htra]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Protease]]
| + | |
| Structural highlights
Function
DEGP_ECOLI DegP acts as a chaperone at low temperatures but switches to a peptidase (heat shock protein) at higher temperatures. It degrades transiently denatured and unfolded proteins which accumulate in the periplasm following heat shock or other stress conditions. DegP is efficient with Val-Xaa and Ile-Xaa peptide bonds, suggesting a preference for beta-branched side chain amino acids. Only unfolded proteins devoid of disulfide bonds appear capable of being cleaved, thereby preventing non-specific proteolysis of folded proteins. Its proteolytic activity is essential for the survival of cells at elevated temperatures. It can degrade IciA, ada, casein, globin and PapA. DegP shares specificity with DegQ. DegP is also involved in the biogenesis of partially folded outer-membrane proteins (OMP).[1] [2] [3] [4] [5] [6]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
HtrA proteases are tightly regulated proteolytic assemblies that are essential for maintaining protein homeostasis in extracytosolic compartments. Though HtrA proteases have been characterized in detail, their precise molecular mechanism for switching between different functional states is still unknown. To address this, we carried out biochemical and structural studies of DegP from Escherichia coli. We show that effector-peptide binding to the PDZ domain of DegP induces oligomer conversion from resting hexameric DegP6 into proteolytically active 12-mers and 24-mers (DegP12/24). Moreover, our data demonstrate that a specific protease loop (L3) functions as a conserved molecular switch of HtrA proteases. L3 senses the activation signal-that is, the repositioned PDZ domain of substrate-engaged DegP12/24 or the binding of allosteric effectors to regulatory HtrA proteases such as DegS-and transmits this information to the active site. Implications for protein quality control and regulation of oligomeric enzymes are discussed.
HtrA proteases have a conserved activation mechanism that can be triggered by distinct molecular cues.,Krojer T, Sawa J, Huber R, Clausen T Nat Struct Mol Biol. 2010 Jul;17(7):844-52. Epub 2010 Jun 27. PMID:20581825[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Lipinska B, Zylicz M, Georgopoulos C. The HtrA (DegP) protein, essential for Escherichia coli survival at high temperatures, is an endopeptidase. J Bacteriol. 1990 Apr;172(4):1791-7. PMID:2180903
- ↑ Kolmar H, Waller PR, Sauer RT. The DegP and DegQ periplasmic endoproteases of Escherichia coli: specificity for cleavage sites and substrate conformation. J Bacteriol. 1996 Oct;178(20):5925-9. PMID:8830688
- ↑ Spiess C, Beil A, Ehrmann M. A temperature-dependent switch from chaperone to protease in a widely conserved heat shock protein. Cell. 1999 Apr 30;97(3):339-47. PMID:10319814
- ↑ Krojer T, Pangerl K, Kurt J, Sawa J, Stingl C, Mechtler K, Huber R, Ehrmann M, Clausen T. Interplay of PDZ and protease domain of DegP ensures efficient elimination of misfolded proteins. Proc Natl Acad Sci U S A. 2008 Jun 3;105(22):7702-7. doi:, 10.1073/pnas.0803392105. Epub 2008 May 27. PMID:18505836 doi:10.1073/pnas.0803392105
- ↑ Pan KL, Hsiao HC, Weng CL, Wu MS, Chou CP. Roles of DegP in prevention of protein misfolding in the periplasm upon overexpression of penicillin acylase in Escherichia coli. J Bacteriol. 2003 May;185(10):3020-30. PMID:12730160
- ↑ Krojer T, Sawa J, Schafer E, Saibil HR, Ehrmann M, Clausen T. Structural basis for the regulated protease and chaperone function of DegP. Nature. 2008 Jun 12;453(7197):885-90. Epub 2008 May 21. PMID:18496527 doi:10.1038/nature07004
- ↑ Krojer T, Sawa J, Huber R, Clausen T. HtrA proteases have a conserved activation mechanism that can be triggered by distinct molecular cues. Nat Struct Mol Biol. 2010 Jul;17(7):844-52. Epub 2010 Jun 27. PMID:20581825 doi:http://dx.doi.org/10.1038/nsmb.1840
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