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Connecting the Sequ...
Connecting the Sequence-Space of Bacterial Signaling Proteins to Phenotypes Using Coevolutionary Landscapes
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- Cheng, R. R. (författare)
- Rice Univ, Ctr Theoret Biol Phys, Houston, TX 77005 USA.
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- Nordesjö, O. (författare)
- Uppsala universitet,Institutionen för cell- och molekylärbiologi
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- Hayes, R. L. (författare)
- Univ Michigan, Dept Biophys, Ann Arbor, MI 48109 USA.
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- Levine, H. (författare)
- Rice Univ, Ctr Theoret Biol Phys, Houston, TX 77005 USA.;Rice Univ, Dept Bioengn, Houston, TX USA.
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- Flores, S. C. (författare)
- Uppsala Univ, Dept Cell & Mol Biol, Uppsala, Sweden.
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- Onuchic, J. N. (författare)
- Rice Univ, Ctr Theoret Biol Phys, Houston, TX 77005 USA.;Rice Univ, Dept Phys & Astron, Houston, TX 77005 USA.;Rice Univ, Dept Chem & Biosci, Houston, TX 77005 USA.
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- Morcos, F. (författare)
- Univ Texas Dallas, Dept Biol Sci, Dallas, TX 75080 USA.;Univ Texas Dallas, Ctr Syst Biol, Dallas, TX 75080 USA.
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Rice Univ, Ctr Theoret Biol Phys, Houston, TX 77005 USA Institutionen för cell- och molekylärbiologi (creator_code:org_t)
- 2016-09-07
- 2016
- Engelska.
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Ingår i: Molecular biology and evolution. - : Oxford University Press (OUP). - 0737-4038 .- 1537-1719. ; 33:12, s. 3054-3064
- Relaterad länk:
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https://uu.diva-port... (primary) (Raw object)
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https://academic.oup...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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 20 4 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.
Ämnesord
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Nyckelord
- statistical inference
- mutational phenotypes
- interaction specificity
- epistasis
- fitness landscape
- bacterial signaling
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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