ArticleNucleic acids research2012
Novel insights from hybrid LacI/GalR proteins: family-wide functional attributes and biologically significant variation in transcription repression.
Article in Nucleic acids research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 91 citations in OpenAlex.
- Distinct energetic blueprints diversify function of conserved protein folds.Nature chemistry · 2026Article
- Expanding salivary biomarker detection by creating a synthetic neuraminic acid sensor via chimeragenesis.Applied and environmental microbiology · 2026Article
- Expanding the toolkit of LacI/GalR chimeras.PloS one · 2026Article
- Biological Switches: Past and Future Milestones of Transcription Factor-Based Biosensors.ACS synthetic biology · 2025Review
- Insights into the regulatory mechanisms and application prospects of the transcription factor Cra.Applied and environmental microbiology · 2024Review
- Highly multiplexed design of an allosteric transcription factor to sense new ligands.Nature communications · 2024Article
- Fundamentals and Exceptions of the LysR-type Transcriptional Regulators.ACS synthetic biology · 2024Review
- 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
- Rheostatic contributions to protein stability can obscure a position's functional role.Protein science : a publication of the Protein Society · 2024Article
- Highly multiplexed design of an allosteric transcription factor to sense novel ligands.bioRxiv : the preprint server for biology · 2024Article
- Rugged fitness landscapes minimize promiscuity in the evolution of transcriptional repressors.Cell systems · 2024Article
- Rheostats, toggles, and neutrals, Oh my! A new framework for understanding how amino acid changes modulate protein function.The Journal of biological chemistry · 2024Review
- The intrinsically disordered transcriptional activation domain of CIITA is functionally tuneable by single substitutions: An exception or a new paradigm?Protein science : a publication of the Protein Society · 2024Article
- Accelerating Genetic Sensor Development, Scale-up, and Deployment Using Synthetic Biology.Biodesign research · 2024Article
- Fructose-1-kinase has pleiotropic roles inbioRxiv : the preprint server for biology · 2023Article
- Next generation synthetic memory via intercepting recombinase function.Nature communications · 2023Article
- HPr prevents FruR-mediated facilitation of RNA polymerase binding to the fru promoter in Vibrio cholerae.Nucleic acids research · 2023Article
- Article
- Chimeric MerR-Family Regulators and Logic Elements for the Design of Metal Sensitive Genetic Circuits inACS synthetic biology · 2023Article
- Ligand-specific changes in conformational flexibility mediate long-range allostery in the lac repressor.Nature communications · 2023Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
LacI/GalR transcription regulators have extensive, non-conserved interfaces between their regulatory domains and the 18 amino acids that serve as 'linkers' to their DNA-binding domains. These non-conserved interfaces might contribute to functional differences between paralogs. Previously, two chimeras created by domain recombination displayed novel functional properties. Here, we present a synthetic protein family, which was created by joining the LacI DNA-binding domain/linker to seven additional regulatory domains. Despite 'mismatched' interfaces, chimeras maintained allosteric response to their cognate effectors. Therefore, allostery in many LacI/GalR proteins does not require interfaces with precisely matched interactions. Nevertheless, the chimeric interfaces were not silent to mutagenesis, and preliminary comparisons suggest that the chimeras provide an ideal context for systematically exploring functional contributions of non-conserved positions. DNA looping experiments revealed higher order (dimer-dimer) oligomerization in several chimeras, which might be possible for the natural paralogs. Finally, the biological significance of repression differences was determined by measuring bacterial growth rates on lactose minimal media. Unexpectedly, moderate and strong repressors showed an apparent induction phase, even though inducers were not provided; therefore, an unknown mechanism might contribute to regulation of the lac operon. Nevertheless, altered growth correlated with altered repression, which indicates that observed functional modifications are significant.
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Registered trials
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.