OMP Peptides Modulate the Activity of DegS Protease by Differential Binding to Active and Inactive Conformations
Upon sensing misfolded outer-membrane porins (OMPs) in the periplasm, the E. coli DegS protease cleaves RseA, a transmembrane regulator, transmitting a signal to activate cytoplasmic gene expression. Misfolding is detected by binding of normally inaccessible OMP sequences to the DegS-PDZ domain, whi...
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| Format: | Article |
| Language: | en_US |
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Elsevier B.V.
2015
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| Online Access: | http://hdl.handle.net/1721.1/96365 https://orcid.org/0000-0002-1719-5399 |
| _version_ | 1826218128883843072 |
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| author | Sohn, Jungsan Sauer, Robert T |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Sohn, Jungsan Sauer, Robert T |
| author_sort | Sohn, Jungsan |
| collection | MIT |
| description | Upon sensing misfolded outer-membrane porins (OMPs) in the periplasm, the E. coli DegS protease cleaves RseA, a transmembrane regulator, transmitting a signal to activate cytoplasmic gene expression. Misfolding is detected by binding of normally inaccessible OMP sequences to the DegS-PDZ domain, which relieves allosteric inhibition and activates proteolysis. Here we show that DegS stimulation can be regulated by OMP peptide affinity for the active and for the inactive protease conformations, as well as by preferential substrate binding to active DegS. Based on the effects of mutations in the peptide-binding pocket of the PDZ domain and elsewhere, we suggest an allosteric pathway that links peptide binding to DegS activation. These results explain fast responses to envelope stress; demonstrate that the protein-unfolding response, even under catastrophic conditions, can be tailored by the peptide sequences that become accessible to DegS; and suggest strategies for control of related PDZ proteases by allosteric effectors. |
| first_indexed | 2024-09-23T17:14:39Z |
| format | Article |
| id | mit-1721.1/96365 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T17:14:39Z |
| publishDate | 2015 |
| publisher | Elsevier B.V. |
| record_format | dspace |
| spelling | mit-1721.1/963652022-09-30T00:39:10Z OMP Peptides Modulate the Activity of DegS Protease by Differential Binding to Active and Inactive Conformations Sohn, Jungsan Sauer, Robert T Massachusetts Institute of Technology. Department of Biology Sohn, Jungsan Sauer, Robert T. Upon sensing misfolded outer-membrane porins (OMPs) in the periplasm, the E. coli DegS protease cleaves RseA, a transmembrane regulator, transmitting a signal to activate cytoplasmic gene expression. Misfolding is detected by binding of normally inaccessible OMP sequences to the DegS-PDZ domain, which relieves allosteric inhibition and activates proteolysis. Here we show that DegS stimulation can be regulated by OMP peptide affinity for the active and for the inactive protease conformations, as well as by preferential substrate binding to active DegS. Based on the effects of mutations in the peptide-binding pocket of the PDZ domain and elsewhere, we suggest an allosteric pathway that links peptide binding to DegS activation. These results explain fast responses to envelope stress; demonstrate that the protein-unfolding response, even under catastrophic conditions, can be tailored by the peptide sequences that become accessible to DegS; and suggest strategies for control of related PDZ proteases by allosteric effectors. National Institutes of Health (U.S.) (NIH grant AI-16892) National Institutes of Health (U.S.) (NIH postdoctoral fellowship (AI-074245-01A1)) 2015-04-02T20:38:15Z 2015-04-02T20:38:15Z 2009-01 2008-10 Article http://purl.org/eprint/type/JournalArticle 10972765 http://hdl.handle.net/1721.1/96365 Sohn, Jungsan, and Robert T. Sauer. “OMP Peptides Modulate the Activity of DegS Protease by Differential Binding to Active and Inactive Conformations.” Molecular Cell 33, no. 1 (January 2009): 64–74. © 2009 Elsevier Inc. https://orcid.org/0000-0002-1719-5399 en_US http://dx.doi.org/10.1016/j.molcel.2008.12.017 Molecular Cell Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Elsevier B.V. Elsevier |
| spellingShingle | Sohn, Jungsan Sauer, Robert T OMP Peptides Modulate the Activity of DegS Protease by Differential Binding to Active and Inactive Conformations |
| title | OMP Peptides Modulate the Activity of DegS Protease by Differential Binding to Active and Inactive Conformations |
| title_full | OMP Peptides Modulate the Activity of DegS Protease by Differential Binding to Active and Inactive Conformations |
| title_fullStr | OMP Peptides Modulate the Activity of DegS Protease by Differential Binding to Active and Inactive Conformations |
| title_full_unstemmed | OMP Peptides Modulate the Activity of DegS Protease by Differential Binding to Active and Inactive Conformations |
| title_short | OMP Peptides Modulate the Activity of DegS Protease by Differential Binding to Active and Inactive Conformations |
| title_sort | omp peptides modulate the activity of degs protease by differential binding to active and inactive conformations |
| url | http://hdl.handle.net/1721.1/96365 https://orcid.org/0000-0002-1719-5399 |
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