Heme controls the structural rearrangement of its sensor protein mediating the hemolytic bacterial survival
Autor: | Yoshitsugu Shiro, Hitomi Sawai, Takehiko Tosha, Satoru Nagatoishi, Hiroshi Sugimoto, Megumi Nishinaga, Yudai Nishitani, Kouhei Tsumoto, Shigetoshi Aono, Seina Nagai, Norifumi Muraki |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
QH301-705.5 Medicine (miscellaneous) Heme medicine.disease_cause Hemolysis General Biochemistry Genetics and Molecular Biology Article Streptococcus agalactiae Bioinorganic chemistry 03 medical and health sciences chemistry.chemical_compound Bacterial Proteins medicine Biology (General) Transcription factor X-ray crystallography 030102 biochemistry & molecular biology biology DNA-binding domain biology.organism_classification medicine.disease respiratory tract diseases 030104 developmental biology Biochemistry chemistry Hemoglobin General Agricultural and Biological Sciences DNA Bacteria |
Zdroj: | Communications Biology Communications Biology, Vol 4, Iss 1, Pp 1-12 (2021) |
ISSN: | 2399-3642 |
Popis: | Hemes (iron-porphyrins) are critical for biological processes in all organisms. Hemolytic bacteria survive by acquiring b-type heme from hemoglobin in red blood cells from their animal hosts. These bacteria avoid the cytotoxicity of excess heme during hemolysis by expressing heme-responsive sensor proteins that act as transcriptional factors to regulate the heme efflux system in response to the cellular heme concentration. Here, the underlying regulatory mechanisms were investigated using crystallographic, spectroscopic, and biochemical studies to understand the structural basis of the heme-responsive sensor protein PefR from Streptococcus agalactiae, a causative agent of neonatal life-threatening infections. Structural comparison of heme-free PefR, its complex with a target DNA, and heme-bound PefR revealed that unique heme coordination controls a >20 Å structural rearrangement of the DNA binding domains to dissociate PefR from the target DNA. We also found heme-bound PefR stably binds exogenous ligands, including carbon monoxide, a by-product of the heme degradation reaction. Nishinaga et al. present structural characterization of the transcription regulator PefR from S. agalactiae in different states (apo-, DNAbound, heme-bound, CO-heme-bound and CN-heme-bound-PefRs). Structural comparison revealed that unique heme coordination controls structural rearrangement for the survival of the neonatal infection-causing hemolytic bacteria. |
Databáze: | OpenAIRE |
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