Structural Basis of a Rationally Rewired Protein-Protein Interface Critical to Bacterial Signaling
Two-component signal transduction systems typically involve a sensor histidine kinase that specifically phosphorylates a single, cognate response regulator. This protein-protein interaction relies on molecular recognition via a small set of residues in each protein. To better understand how these re...
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| Format: | Article |
| Language: | en_US |
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Elsevier
2017
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| Online Access: | http://hdl.handle.net/1721.1/110413 https://orcid.org/0000-0002-8288-7607 |
| _version_ | 1826188018787024896 |
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| author | Casino, Patricia Marina, Alberto Podgornaia, Anna Igorevna Laub, Michael T |
| author2 | Massachusetts Institute of Technology. Computational and Systems Biology Program |
| author_facet | Massachusetts Institute of Technology. Computational and Systems Biology Program Casino, Patricia Marina, Alberto Podgornaia, Anna Igorevna Laub, Michael T |
| author_sort | Casino, Patricia |
| collection | MIT |
| description | Two-component signal transduction systems typically involve a sensor histidine kinase that specifically phosphorylates a single, cognate response regulator. This protein-protein interaction relies on molecular recognition via a small set of residues in each protein. To better understand how these residues determine the specificity of kinase-substrate interactions, we rationally rewired the interaction interface of a Thermotoga maritima two-component system, HK853-RR468, to match that found in a different two-component system, Escherichia coli PhoR-PhoB. The rewired proteins interacted robustly with each other, but no longer interacted with the parent proteins. Analysis of the crystal structures of the wild-type and mutant protein complexes and a systematic mutagenesis study reveal how individual mutations contribute to the rewiring of interaction specificity. Our approach and conclusions have implications for studies of other protein-protein interactions and protein evolution and for the design of novel protein interfaces. |
| first_indexed | 2024-09-23T07:53:21Z |
| format | Article |
| id | mit-1721.1/110413 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T07:53:21Z |
| publishDate | 2017 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/1104132022-09-30T00:49:12Z Structural Basis of a Rationally Rewired Protein-Protein Interface Critical to Bacterial Signaling Casino, Patricia Marina, Alberto Podgornaia, Anna Igorevna Laub, Michael T Massachusetts Institute of Technology. Computational and Systems Biology Program Massachusetts Institute of Technology. Department of Biology Podgornaia, Anna Igorevna Laub, Michael T Two-component signal transduction systems typically involve a sensor histidine kinase that specifically phosphorylates a single, cognate response regulator. This protein-protein interaction relies on molecular recognition via a small set of residues in each protein. To better understand how these residues determine the specificity of kinase-substrate interactions, we rationally rewired the interaction interface of a Thermotoga maritima two-component system, HK853-RR468, to match that found in a different two-component system, Escherichia coli PhoR-PhoB. The rewired proteins interacted robustly with each other, but no longer interacted with the parent proteins. Analysis of the crystal structures of the wild-type and mutant protein complexes and a systematic mutagenesis study reveal how individual mutations contribute to the rewiring of interaction specificity. Our approach and conclusions have implications for studies of other protein-protein interactions and protein evolution and for the design of novel protein interfaces. National Institutes of Health (U.S.) (MCB-0844442) 2017-07-03T12:51:40Z 2017-07-03T12:51:40Z 2013-08 2013-06 Article http://purl.org/eprint/type/JournalArticle 0969-2126 1878-4186 http://hdl.handle.net/1721.1/110413 Podgornaia, Anna I.; Casino, Patricia; Marina, Alberto and Laub, Michael T. “Structural Basis of a Rationally Rewired Protein-Protein Interface Critical to Bacterial Signaling.” Structure 21, no. 9 (September 2013): 1636–1647 © 2013 Elsevier Ltd https://orcid.org/0000-0002-8288-7607 en_US http://dx.doi.org/10.1016/j.str.2013.07.005 Structure Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier PMC |
| spellingShingle | Casino, Patricia Marina, Alberto Podgornaia, Anna Igorevna Laub, Michael T Structural Basis of a Rationally Rewired Protein-Protein Interface Critical to Bacterial Signaling |
| title | Structural Basis of a Rationally Rewired Protein-Protein Interface Critical to Bacterial Signaling |
| title_full | Structural Basis of a Rationally Rewired Protein-Protein Interface Critical to Bacterial Signaling |
| title_fullStr | Structural Basis of a Rationally Rewired Protein-Protein Interface Critical to Bacterial Signaling |
| title_full_unstemmed | Structural Basis of a Rationally Rewired Protein-Protein Interface Critical to Bacterial Signaling |
| title_short | Structural Basis of a Rationally Rewired Protein-Protein Interface Critical to Bacterial Signaling |
| title_sort | structural basis of a rationally rewired protein protein interface critical to bacterial signaling |
| url | http://hdl.handle.net/1721.1/110413 https://orcid.org/0000-0002-8288-7607 |
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