A Conserved Activation Cluster Is Required for Allosteric Communication in HtrA-Family Proteases
In E. coli, outer-membrane stress causes a transcriptional response through a signaling cascade initiated by DegS cleavage of a transmembrane anti-sigma factor. Each subunit of DegS, an HtrAfamily protease, contains a protease domain and a PDZ domain. The trimeric protease domain is autoinhibited b...
| Main Authors: | , , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
Elsevier
2017
|
| Online Access: | http://hdl.handle.net/1721.1/106341 |
| _version_ | 1811085977019482112 |
|---|---|
| author | de Regt, Anna K. Kim, Seokhee Sohn, Jungsan Grant, Robert A. Baker, Tania A. |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology de Regt, Anna K. Kim, Seokhee Sohn, Jungsan Grant, Robert A. Baker, Tania A. |
| author_sort | de Regt, Anna K. |
| collection | MIT |
| description | In E. coli, outer-membrane stress causes a transcriptional response through a signaling cascade initiated by DegS cleavage of a transmembrane anti-sigma factor. Each subunit of DegS, an HtrAfamily protease, contains a protease domain and a PDZ domain. The trimeric protease domain is
autoinhibited by the unliganded PDZ domains. Allosteric activation requires binding of unassembled outer-membrane proteins (OMPs) to the PDZ domains and protein-substrate binding. Here, we identify a set of DegS residues that cluster together at subunit-subunit interfaces in the
trimer, link the active sites and substrate-binding sites, and are crucial for stabilizing the active enzyme conformation in response to OMP signaling. These residues are conserved across the HtrA-protease family, including orthologs linked to human disease, supporting a common
mechanism of allosteric activation. Indeed, mutation of residues at homologous positions in the DegP quality-control protease also eliminates allosteric activation. |
| first_indexed | 2024-09-23T13:18:57Z |
| format | Article |
| id | mit-1721.1/106341 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T13:18:57Z |
| publishDate | 2017 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/1063412022-09-28T13:21:05Z A Conserved Activation Cluster Is Required for Allosteric Communication in HtrA-Family Proteases de Regt, Anna K. Kim, Seokhee Sohn, Jungsan Grant, Robert A. Baker, Tania A. Massachusetts Institute of Technology. Department of Biology In E. coli, outer-membrane stress causes a transcriptional response through a signaling cascade initiated by DegS cleavage of a transmembrane anti-sigma factor. Each subunit of DegS, an HtrAfamily protease, contains a protease domain and a PDZ domain. The trimeric protease domain is autoinhibited by the unliganded PDZ domains. Allosteric activation requires binding of unassembled outer-membrane proteins (OMPs) to the PDZ domains and protein-substrate binding. Here, we identify a set of DegS residues that cluster together at subunit-subunit interfaces in the trimer, link the active sites and substrate-binding sites, and are crucial for stabilizing the active enzyme conformation in response to OMP signaling. These residues are conserved across the HtrA-protease family, including orthologs linked to human disease, supporting a common mechanism of allosteric activation. Indeed, mutation of residues at homologous positions in the DegP quality-control protease also eliminates allosteric activation. National Institutes of Health (U.S.) (Grant AI-16892) Charles A. King Trust (Postdoctoral Fellowship) 2017-01-11T17:08:46Z 2017-01-11T17:08:46Z 2015-02 2015-01 Article http://purl.org/eprint/type/JournalArticle 0969-2126 1878-4186 http://hdl.handle.net/1721.1/106341 de Regt, Anna K. et al. “A Conserved Activation Cluster Is Required for Allosteric Communication in HtrA-Family Proteases.” Structure 23.3 (2015): 517–526. en_US http://dx.doi.org/10.1016/j.str.2015.01.012 Structure Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier PMC |
| spellingShingle | de Regt, Anna K. Kim, Seokhee Sohn, Jungsan Grant, Robert A. Baker, Tania A. A Conserved Activation Cluster Is Required for Allosteric Communication in HtrA-Family Proteases |
| title | A Conserved Activation Cluster Is Required for Allosteric Communication in HtrA-Family Proteases |
| title_full | A Conserved Activation Cluster Is Required for Allosteric Communication in HtrA-Family Proteases |
| title_fullStr | A Conserved Activation Cluster Is Required for Allosteric Communication in HtrA-Family Proteases |
| title_full_unstemmed | A Conserved Activation Cluster Is Required for Allosteric Communication in HtrA-Family Proteases |
| title_short | A Conserved Activation Cluster Is Required for Allosteric Communication in HtrA-Family Proteases |
| title_sort | conserved activation cluster is required for allosteric communication in htra family proteases |
| url | http://hdl.handle.net/1721.1/106341 |
| work_keys_str_mv | AT deregtannak aconservedactivationclusterisrequiredforallostericcommunicationinhtrafamilyproteases AT kimseokhee aconservedactivationclusterisrequiredforallostericcommunicationinhtrafamilyproteases AT sohnjungsan aconservedactivationclusterisrequiredforallostericcommunicationinhtrafamilyproteases AT grantroberta aconservedactivationclusterisrequiredforallostericcommunicationinhtrafamilyproteases AT bakertaniaa aconservedactivationclusterisrequiredforallostericcommunicationinhtrafamilyproteases AT deregtannak conservedactivationclusterisrequiredforallostericcommunicationinhtrafamilyproteases AT kimseokhee conservedactivationclusterisrequiredforallostericcommunicationinhtrafamilyproteases AT sohnjungsan conservedactivationclusterisrequiredforallostericcommunicationinhtrafamilyproteases AT grantroberta conservedactivationclusterisrequiredforallostericcommunicationinhtrafamilyproteases AT bakertaniaa conservedactivationclusterisrequiredforallostericcommunicationinhtrafamilyproteases |