ArticleProceedings of the National Academy of Sciences of the United States of America2014
Toward rationally redesigning bacterial two-component signaling systems using coevolutionary information.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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Who cites it
73 citing papers in PubMed, 136 citations in OpenAlex.
- Identification and engineering of highly functional potyviral proteases in cells using co-evolutionary models.Nature communications · 2026Article
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- Impact of phylogeny on the inference of functional sectors from protein sequence data.PLoS computational biology · 2024Article
- Sequence-Based Protein Design: A Review of Using Statistical Models to Characterize Coevolutionary Traits for Developing Hybrid Proteins as Genetic Sensors.International journal of molecular sciences · 2024Review
- Machine learning in biological physics: From biomolecular prediction to design.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Pairing interacting protein sequences using masked language modeling.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Functional effects of mutations in proteins can be predicted and interpreted by guided selection of sequence covariation information.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- The physical and evolutionary energy landscapes of devolved protein sequences corresponding to pseudogenes.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Residue coevolution and mutational landscape for OmpR and NarL response regulator subfamilies.Biophysical journal · 2024Article
- Coevolutionary Information Captures Catalytic Functions and Reveals Divergent Roles of Terpene Synthase Interdomain Connections.Biochemistry · 2024Article
- Evolution shapes interaction patterns for epistasis and specific protein binding in a two-component signaling system.Communications chemistry · 2024Article
- Selection pressures on evolution of ribonuclease H explored with rigorous free-energy-based design.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Photoacoustic Calorimetry Studies of OBiochemistry · 2024Article
- Generating interacting protein sequences using domain-to-domain translation.Bioinformatics (Oxford, England) · 2023Article
- Latent generative landscapes as maps of functional diversity in protein sequence space.Nature communications · 2023Article
- Data-driven design of orthogonal protein-protein interactions.Science signaling · 2023Article
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- Impact of phylogeny on structural contact inference from protein sequence data.Journal of the Royal Society, Interface · 2023Article
13 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A challenge in molecular biology is to distinguish the key subset of residues that allow two-component signaling (TCS) proteins to recognize their correct signaling partner such that they can transiently bind and transfer signal, i.e., phosphoryl group. Detailed knowledge of this information would allow one to search sequence space for mutations that can be used to systematically tune the signal transmission between TCS partners as well as potentially encode a TCS protein to preferentially transfer signals to a nonpartner. Motivated by the notion that this detailed information is found in sequence data, we explore the sequence coevolution between signaling partners to better understand how mutations can positively or negatively alter their ability to transfer signal. Using direct coupling analysis for determining evolutionarily conserved protein-protein interactions, we apply a metric called the direct information score to quantify mutational changes in the interaction between TCS proteins and demonstrate that it accurately correlates with experimental mutagenesis studies probing the mutational change in measured in vitro phosphotransfer. Furthermore, by subtracting from our metric an appropriate null model corresponding to generic, conserved features in TCS signaling pairs, we can isolate the determinants that give rise to interaction specificity and recognition, which are variable among different TCS partners. Our methodology forms a potential framework for the rational design of TCS systems by allowing one to quickly search sequence space for mutations or even entirely new sequences that can increase or decrease our metric, as a proxy for increasing or decreasing phosphotransfer ability between TCS proteins.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.