ArticleThe Journal of biological chemistry2012
Structural basis for the transcriptional regulation of heme homeostasis in Lactococcus lactis.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 77 citations in OpenAlex.
- Advances and perspectives in genetically encoded biosensors for biomarker detection and theranostic circuits.Synthetic and systems biotechnology · 2027Review
- Biosensors for Detection of Labile Heme in Biological Samples.Biosensors · 2025Review
- Heme in Bacterial Pathogenesis and as an Antimicrobial Target.Chemical reviews · 2025Review
- DNA-bound structure of Clostridioides difficile heme-sensing HsmR gives insight on how the unique dimer mode governs DNA specificity in MarR transcriptional regulators.Nucleic acids research · 2025Article
- Bacterial Metallostasis: Metal Sensing, Metalloproteome Remodeling, and Metal Trafficking.Chemical reviews · 2024Review
- Review
- Structures of the DarR transcription regulator reveal unique modes of second messenger and DNA binding.Nature communications · 2023Article
- Heme acquisition and tolerance in Gram-positive model bacteria: An orchestrated balance.Heliyon · 2023Review
- Applications of the Whole-Cell System in the Efficient Biosynthesis of Heme.International journal of molecular sciences · 2023Review
- Heme biosensor-guided in vivo pathway optimization and directed evolution for efficient biosynthesis of heme.Biotechnology for biofuels and bioproducts · 2023Article
- Crystal structures of free and ligand-bound forms of the TetR/AcrR-like regulator SCO3201 from Streptomyces coelicolor suggest a novel allosteric mechanism.The FEBS journal · 2023Article
- Bacterial Transcriptional Regulators: A Road Map for Functional, Structural, and Biophysical Characterization.International journal of molecular sciences · 2022Review
- Heme controls the structural rearrangement of its sensor protein mediating the hemolytic bacterial survival.Communications biology · 2021Article
- Tuning the Binding Affinity of Heme-Responsive Biosensor for Precise and Dynamic Pathway Regulation.iScience · 2020Article
- Genetics of Lactococci.Microbiology spectrum · 2019Review
- Heme sensing and detoxification by HatRT contributes to pathogenesis during Clostridium difficile infection.PLoS pathogens · 2018Article
- Review
- Functional Mechanism of the Efflux Pumps Transcription Regulators FromFrontiers in molecular biosciences · 2018Review
- Adaptation to Aerobic Environment ofFrontiers in microbiology · 2018Article
- Interactive comparison and remediation of collections of macromolecular structures.Protein science : a publication of the Protein Society · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although heme is a crucial element for many biological processes including respiration, heme homeostasis should be regulated strictly due to the cytotoxicity of free heme molecules. Numerous lactic acid bacteria, including Lactococcus lactis, acquire heme molecules exogenously to establish an aerobic respiratory chain. A heme efflux system plays an important role for heme homeostasis to avoid cytotoxicity of acquired free heme, but its regulatory mechanism is not clear. Here, we report that the transcriptional regulator heme-regulated transporter regulator (HrtR) senses and binds a heme molecule as its physiological effector to regulate the expression of the heme-efflux system responsible for heme homeostasis in L. lactis. To elucidate the molecular mechanisms of how HrtR senses a heme molecule and regulates gene expression for the heme efflux system, we determined the crystal structures of the apo-HrtR·DNA complex, apo-HrtR, and holo-HrtR at a resolution of 2.0, 3.1, and 1.9 Å, respectively. These structures revealed that HrtR is a member of the TetR family of transcriptional regulators. The residue pair Arg-46 and Tyr-50 plays a crucial role for specific DNA binding through hydrogen bonding and a CH-π interaction with the DNA bases. HrtR adopts a unique mechanism for its functional regulation upon heme sensing. Heme binding to HrtR causes a coil-to-helix transition of the α4 helix in the heme-sensing domain, which triggers a structural change of HrtR, causing it to dissociate from the target DNA for derepression of the genes encoding the heme efflux system. HrtR uses a unique heme-sensing motif with bis-His (His-72 and His-149) ligation to the heme, which is essential for the coil-to-helix transition of the α4 helix upon heme sensing.
Indexed as
Identifiers
What OpenQuestion holds
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.