Connecting the Sequence-Space of Bacterial Signaling Proteins to Phenotypes Using Coevolutionary Landscapes
| dc.citation.firstpage | 3054 | en_US |
| dc.citation.issueNumber | 12 | en_US |
| dc.citation.journalTitle | Molecular Biology and Evolution | en_US |
| dc.citation.lastpage | 3064 | en_US |
| dc.citation.volumeNumber | 33 | en_US |
| dc.contributor.author | Cheng, R.R. | en_US |
| dc.contributor.author | Nordesjӧ, O. | en_US |
| dc.contributor.author | Hayes, R.L. | en_US |
| dc.contributor.author | Levine, H. | en_US |
| dc.contributor.author | Flores, S.C. | en_US |
| dc.contributor.author | Onuchic, José Nelson | en_US |
| dc.contributor.author | Morcos, F. | en_US |
| dc.contributor.org | Center for Theoretical Biological Physics | en_US |
| dc.date.accessioned | 2017-05-05T19:00:53Z | en_US |
| dc.date.available | 2017-05-05T19:00:53Z | en_US |
| dc.date.issued | 2016 | en_US |
| dc.description.abstract | Two-component signaling (TCS) is the primary means by which bacteria sense and respond to the environment. TCS involves two partner proteins working in tandem, which interact to perform cellular functions whereas limiting interactions with non-partners (i.e., cross-talk). We construct a Potts model for TCS that can quantitatively predict how mutating amino acid identities affect the interaction between TCS partners and non-partners. The parameters of this model are inferred directly from protein sequence data. This approach drastically reduces the computational complexity of exploring the sequence-space of TCS proteins. As a stringent test, we compare its predictions to a recent comprehensive mutational study, which characterized the functionality of 204 mutational variants of the PhoQ kinase in Escherichia coli. We find that our best predictions accurately reproduce the amino acid combinations found in experiment, which enable functional signaling with its partner PhoP. These predictions demonstrate the evolutionary pressure to preserve the interaction between TCS partners as well as prevent unwanted cross-talk. Further, we calculate the mutational change in the binding affinity between PhoQ and PhoP, providing an estimate to the amount of destabilization needed to disrupt TCS. | en_US |
| dc.identifier.citation | Cheng, R.R., Nordesjӧ, O., Hayes, R.L., et al.. "Connecting the Sequence-Space of Bacterial Signaling Proteins to Phenotypes Using Coevolutionary Landscapes." <i>Molecular Biology and Evolution,</i> 33, no. 12 (2016) Oxford University Press: 3054-3064. https://doi.org/10.1093/molbev/msw188. | en_US |
| dc.identifier.doi | https://doi.org/10.1093/molbev/msw188 | en_US |
| dc.identifier.uri | https://hdl.handle.net/1911/94197 | en_US |
| dc.language.iso | eng | en_US |
| dc.publisher | Oxford University Press | en_US |
| dc.rights | This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. | en_US |
| dc.rights.uri | https://creativecommons.org/licenses/by-nc/4.0/ | en_US |
| dc.subject.keyword | statistical inference | en_US |
| dc.subject.keyword | mutational phenotypes | en_US |
| dc.subject.keyword | interaction specificity | en_US |
| dc.subject.keyword | epistasis | en_US |
| dc.subject.keyword | fitness landscape | en_US |
| dc.subject.keyword | bacterial signaling | en_US |
| dc.title | Connecting the Sequence-Space of Bacterial Signaling Proteins to Phenotypes Using Coevolutionary Landscapes | en_US |
| dc.type | Journal article | en_US |
| dc.type.dcmi | Text | en_US |
| dc.type.publication | publisher version | en_US |