DNA binding mechanism of WhiB4 from Mycobacterium tuberculosis
Mycobacterium tuberculosis (Mtb), the pathogen of tuberculosis, has latently infected about one-third of the world's population and may lead to severe clinical symptoms and death. The WhiB4 protein, a transcription factor, plays a crucial role in the survival and pathology of Mtb. WhiB4 leads t...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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KeAi Communications Co. Ltd.
2022-02-01
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| Series: | Magnetic Resonance Letters |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2772516221000103 |
| _version_ | 1798005976906858496 |
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| author | Qiran Zhai Bo Duan Chen Lin Jun Liu Lu Zhang Bin Xia |
| author_facet | Qiran Zhai Bo Duan Chen Lin Jun Liu Lu Zhang Bin Xia |
| author_sort | Qiran Zhai |
| collection | DOAJ |
| description | Mycobacterium tuberculosis (Mtb), the pathogen of tuberculosis, has latently infected about one-third of the world's population and may lead to severe clinical symptoms and death. The WhiB4 protein, a transcription factor, plays a crucial role in the survival and pathology of Mtb. WhiB4 leads to the condensation of mycobacterial nucleoids and regulates the expression of genes involved in central metabolism, respiration, and maintaining redox homeostasis. Here, we report the solution structure of reduced apo-WhiB4 monomer, which consists of an unstructured N-terminal domain with four cysteine residues and a helix-turn-helix C-terminal domain that plays a major role in DNA binding. The C-terminal domain of WhiB4 binds DNA at the minor groove, with five positively charged lysine/arginine residues contacting DNA sugar-phosphate backbones through electrostatic interactions. AT-rich DNA sequences with narrower minor grooves are more preferred by WhiB4. The binding affinity of a single C-terminal domain of WhiB4 is weak. When oxidized, WhiB4 can form dimers and oligomers in different forms through disulfide bonds, which should significantly enhance its DNA binding ability through multivalent effect and change the local structure of target genes and influence their transcription. These structural features form the basis for WhiB4 to function as a redox-sensitive transcription factor in Mtb. |
| first_indexed | 2024-04-11T12:47:33Z |
| format | Article |
| id | doaj.art-84d695d2b3c24b4d9644ee3b836bc651 |
| institution | Directory Open Access Journal |
| issn | 2772-5162 |
| language | English |
| last_indexed | 2024-04-11T12:47:33Z |
| publishDate | 2022-02-01 |
| publisher | KeAi Communications Co. Ltd. |
| record_format | Article |
| series | Magnetic Resonance Letters |
| spelling | doaj.art-84d695d2b3c24b4d9644ee3b836bc6512022-12-22T04:23:18ZengKeAi Communications Co. Ltd.Magnetic Resonance Letters2772-51622022-02-01211727DNA binding mechanism of WhiB4 from Mycobacterium tuberculosisQiran Zhai0Bo Duan1Chen Lin2Jun Liu3Lu Zhang4Bin Xia5Beijing Nuclear Magnetic Resonance Center, College of Chemistry and Molecular Engineering, School of Life Sciences, Peking University, Beijing, 100871, ChinaBeijing Nuclear Magnetic Resonance Center, College of Chemistry and Molecular Engineering, School of Life Sciences, Peking University, Beijing, 100871, ChinaState Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai, 200433, ChinaDepartment of Molecular Genetics, University of Toronto, Toronto, Ontario, M5G 1M1, CanadaState Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai, 200433, ChinaBeijing Nuclear Magnetic Resonance Center, College of Chemistry and Molecular Engineering, School of Life Sciences, Peking University, Beijing, 100871, China; Corresponding author. Beijing Nuclear Magnetic Resonance Center, College of Chemistry and Molecular Engineering, School of Life Sciences, Peking University, Beijing, 100871, China.Mycobacterium tuberculosis (Mtb), the pathogen of tuberculosis, has latently infected about one-third of the world's population and may lead to severe clinical symptoms and death. The WhiB4 protein, a transcription factor, plays a crucial role in the survival and pathology of Mtb. WhiB4 leads to the condensation of mycobacterial nucleoids and regulates the expression of genes involved in central metabolism, respiration, and maintaining redox homeostasis. Here, we report the solution structure of reduced apo-WhiB4 monomer, which consists of an unstructured N-terminal domain with four cysteine residues and a helix-turn-helix C-terminal domain that plays a major role in DNA binding. The C-terminal domain of WhiB4 binds DNA at the minor groove, with five positively charged lysine/arginine residues contacting DNA sugar-phosphate backbones through electrostatic interactions. AT-rich DNA sequences with narrower minor grooves are more preferred by WhiB4. The binding affinity of a single C-terminal domain of WhiB4 is weak. When oxidized, WhiB4 can form dimers and oligomers in different forms through disulfide bonds, which should significantly enhance its DNA binding ability through multivalent effect and change the local structure of target genes and influence their transcription. These structural features form the basis for WhiB4 to function as a redox-sensitive transcription factor in Mtb.http://www.sciencedirect.com/science/article/pii/S2772516221000103WhiB4Mycobacterium tuberculosisSolution structureDNA binding mechanism |
| spellingShingle | Qiran Zhai Bo Duan Chen Lin Jun Liu Lu Zhang Bin Xia DNA binding mechanism of WhiB4 from Mycobacterium tuberculosis Magnetic Resonance Letters WhiB4 Mycobacterium tuberculosis Solution structure DNA binding mechanism |
| title | DNA binding mechanism of WhiB4 from Mycobacterium tuberculosis |
| title_full | DNA binding mechanism of WhiB4 from Mycobacterium tuberculosis |
| title_fullStr | DNA binding mechanism of WhiB4 from Mycobacterium tuberculosis |
| title_full_unstemmed | DNA binding mechanism of WhiB4 from Mycobacterium tuberculosis |
| title_short | DNA binding mechanism of WhiB4 from Mycobacterium tuberculosis |
| title_sort | dna binding mechanism of whib4 from mycobacterium tuberculosis |
| topic | WhiB4 Mycobacterium tuberculosis Solution structure DNA binding mechanism |
| url | http://www.sciencedirect.com/science/article/pii/S2772516221000103 |
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