Toward rationally redesigning bacterial two-component signaling systems using coevolutionary information
Identifieur interne : 000168 ( Main/Exploration ); précédent : 000167; suivant : 000169Toward rationally redesigning bacterial two-component signaling systems using coevolutionary information
Auteurs : Ryan R. Cheng ; Faruck Morcos ; Herbert Levine ; José N. OnuchicSource :
- Proceedings of the National Academy of Sciences of the United States of America [ 0027-8424 ] ; 2014.
Abstract
Our study uses amino acid coevolutionary information to better understand how bacterial two-component signaling (TCS) proteins preferentially interact with their correct partners while avoiding interactions with nonpartners. We extract coevolutionary couplings from sequences of TCS partners and study how coevolution is necessary to maintain their ability to transfer signals with high specificity. We use these coevolving couplings to devise a metric, which can predict the effects of mutations in the quality of signal transmission observed in vitro and provide support to the hypothesis that hybrid TCS proteins have reduced specificity. Our metric can potentially be used to redesign a TCS protein to preferentially interact with a nonpartner. Furthermore, our study can potentially be extended to networks of interacting proteins.
Url:
DOI: 10.1073/pnas.1323734111
PubMed: 24449878
PubMed Central: 3918776
Affiliations:
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Cheng</name><affiliation><nlm:aff wicri:cut=", and" id="aff1">Center for Theoretical Biological Physics</nlm:aff></affiliation></author><author><name sortKey="Morcos, Faruck" sort="Morcos, Faruck" uniqKey="Morcos F" first="Faruck" last="Morcos">Faruck Morcos</name><affiliation><nlm:aff wicri:cut=", and" id="aff1">Center for Theoretical Biological Physics</nlm:aff></affiliation></author><author><name sortKey="Levine, Herbert" sort="Levine, Herbert" uniqKey="Levine H" first="Herbert" last="Levine">Herbert Levine</name><affiliation><nlm:aff wicri:cut=", and" id="aff1">Center for Theoretical Biological Physics</nlm:aff></affiliation><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Onuchic, Jose N" sort="Onuchic, Jose N" uniqKey="Onuchic J" first="José N." last="Onuchic">José N. Onuchic</name><affiliation><nlm:aff wicri:cut=", and" id="aff1">Center for Theoretical Biological Physics</nlm:aff></affiliation><affiliation><nlm:aff id="aff3">Physics and Astronomy,<institution>Rice University</institution>, Houston,<addr-line>TX</addr-line> 77005</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">24449878</idno><idno type="pmc">3918776</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3918776</idno><idno type="RBID">PMC:3918776</idno><idno type="doi">10.1073/pnas.1323734111</idno><date when="2014">2014</date><idno type="wicri:Area/Pmc/Corpus">000407</idno><idno type="wicri:Area/Pmc/Curation">000407</idno><idno type="wicri:Area/Pmc/Checkpoint">000158</idno><idno type="wicri:Area/Ncbi/Merge">000493</idno><idno type="wicri:Area/Ncbi/Curation">000493</idno><idno type="wicri:Area/Ncbi/Checkpoint">000493</idno><idno type="wicri:doubleKey">0027-8424:2014:Cheng R:toward:rationally:redesigning</idno><idno type="wicri:Area/Main/Merge">000168</idno><idno type="wicri:Area/Main/Curation">000168</idno><idno type="wicri:Area/Main/Exploration">000168</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Toward rationally redesigning bacterial two-component signaling systems using coevolutionary information</title><author><name sortKey="Cheng, Ryan R" sort="Cheng, Ryan R" uniqKey="Cheng R" first="Ryan R." last="Cheng">Ryan R. Cheng</name><affiliation><nlm:aff wicri:cut=", and" id="aff1">Center for Theoretical Biological Physics</nlm:aff></affiliation></author><author><name sortKey="Morcos, Faruck" sort="Morcos, Faruck" uniqKey="Morcos F" first="Faruck" last="Morcos">Faruck Morcos</name><affiliation><nlm:aff wicri:cut=", and" id="aff1">Center for Theoretical Biological Physics</nlm:aff></affiliation></author><author><name sortKey="Levine, Herbert" sort="Levine, Herbert" uniqKey="Levine H" first="Herbert" last="Levine">Herbert Levine</name><affiliation><nlm:aff wicri:cut=", and" id="aff1">Center for Theoretical Biological Physics</nlm:aff></affiliation><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Onuchic, Jose N" sort="Onuchic, Jose N" uniqKey="Onuchic J" first="José N." last="Onuchic">José N. Onuchic</name><affiliation><nlm:aff wicri:cut=", and" id="aff1">Center for Theoretical Biological Physics</nlm:aff></affiliation><affiliation><nlm:aff id="aff3">Physics and Astronomy,<institution>Rice University</institution>, Houston,<addr-line>TX</addr-line> 77005</nlm:aff></affiliation></author></analytic><series><title level="j">Proceedings of the National Academy of Sciences of the United States of America</title><idno type="ISSN">0027-8424</idno><idno type="eISSN">1091-6490</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>Significance</title><p>Our study uses amino acid coevolutionary information to better understand how bacterial two-component signaling (TCS) proteins preferentially interact with their correct partners while avoiding interactions with nonpartners. We extract coevolutionary couplings from sequences of TCS partners and study how coevolution is necessary to maintain their ability to transfer signals with high specificity. We use these coevolving couplings to devise a metric, which can predict the effects of mutations in the quality of signal transmission observed in vitro and provide support to the hypothesis that hybrid TCS proteins have reduced specificity. Our metric can potentially be used to redesign a TCS protein to preferentially interact with a nonpartner. Furthermore, our study can potentially be extended to networks of interacting proteins.</p></div></front></TEI><affiliations><list></list><tree><noCountry><name sortKey="Cheng, Ryan R" sort="Cheng, Ryan R" uniqKey="Cheng R" first="Ryan R." last="Cheng">Ryan R. Cheng</name><name sortKey="Levine, Herbert" sort="Levine, Herbert" uniqKey="Levine H" first="Herbert" last="Levine">Herbert Levine</name><name sortKey="Morcos, Faruck" sort="Morcos, Faruck" uniqKey="Morcos F" first="Faruck" last="Morcos">Faruck Morcos</name><name sortKey="Onuchic, Jose N" sort="Onuchic, Jose N" uniqKey="Onuchic J" first="José N." last="Onuchic">José N. Onuchic</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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