Chasing the structural diversity of the transcription regulator Mycobacterium tuberculosis HigA2
Transcription factors are the primary regulators of gene expression and recognize specific DNA sequences under diverse physiological conditions. Although they are vital for many important cellular processes, it remains unclear when and how transcription factors and DNA interact. The antitoxin from a...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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International Union of Crystallography
2021-09-01
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| Series: | IUCrJ |
| Subjects: | |
| Online Access: | http://scripts.iucr.org/cgi-bin/paper?S2052252521007715 |
| _version_ | 1828130098017992704 |
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| author | William Richardson Gyun Won Kang Hee Joong Lee Kang Mu Kwon Saron Kim Hyo Jung Kim |
| author_facet | William Richardson Gyun Won Kang Hee Joong Lee Kang Mu Kwon Saron Kim Hyo Jung Kim |
| author_sort | William Richardson |
| collection | DOAJ |
| description | Transcription factors are the primary regulators of gene expression and recognize specific DNA sequences under diverse physiological conditions. Although they are vital for many important cellular processes, it remains unclear when and how transcription factors and DNA interact. The antitoxin from a toxin–antitoxin system is an example of negative transcriptional autoregulation: during expression of the cognate toxin it is suppressed through binding to a specific DNA sequence. In the present study, the antitoxin HigA2 from Mycobacterium tuberculosis M37Rv was structurally examined. The crystal structure of M. tuberculosis HigA2 comprises three sections: an N-terminal autocleavage region, an α-helix bundle which contains an HTH motif, and a C-terminal β-lid. The N-terminal region is responsible for toxin binding, but was shown to cleave spontaneously in its absence. The HTH motif performs a key role in DNA binding, with the C-terminal β-lid influencing the interaction by mediating the distance between the motifs. However, M. tuberculosis HigA2 exhibits a unique coordination of the HTH motif and no DNA-binding activity is detected. Three crystal structures of M. tuberculosis HigA2 show a flexible alignment of the HTH motif, which implies that the motif undergoes structural rearrangement to interact with DNA. This study reveals the molecular mechanisms of how transcription factors interact with partner proteins or DNA. |
| first_indexed | 2024-04-11T16:29:39Z |
| format | Article |
| id | doaj.art-ba293b1fee3043e3a81a509a24023778 |
| institution | Directory Open Access Journal |
| issn | 2052-2525 |
| language | English |
| last_indexed | 2024-04-11T16:29:39Z |
| publishDate | 2021-09-01 |
| publisher | International Union of Crystallography |
| record_format | Article |
| series | IUCrJ |
| spelling | doaj.art-ba293b1fee3043e3a81a509a240237782022-12-22T04:14:05ZengInternational Union of CrystallographyIUCrJ2052-25252021-09-018582383210.1107/S2052252521007715lz5052Chasing the structural diversity of the transcription regulator Mycobacterium tuberculosis HigA2William Richardson0Gyun Won Kang1Hee Joong Lee2Kang Mu Kwon3Saron Kim4Hyo Jung Kim5Centre for Biomolecular Sciences, School of Pharmacy, University of Nottingham, Nottingham, United KingdomCollege of Pharmacy, Woosuk University, Wanju 55338, Republic of KoreaCollege of Pharmacy, Woosuk University, Wanju 55338, Republic of KoreaCollege of Pharmacy, Woosuk University, Wanju 55338, Republic of KoreaCollege of Pharmacy, Woosuk University, Wanju 55338, Republic of KoreaCentre for Biomolecular Sciences, School of Pharmacy, University of Nottingham, Nottingham, United KingdomTranscription factors are the primary regulators of gene expression and recognize specific DNA sequences under diverse physiological conditions. Although they are vital for many important cellular processes, it remains unclear when and how transcription factors and DNA interact. The antitoxin from a toxin–antitoxin system is an example of negative transcriptional autoregulation: during expression of the cognate toxin it is suppressed through binding to a specific DNA sequence. In the present study, the antitoxin HigA2 from Mycobacterium tuberculosis M37Rv was structurally examined. The crystal structure of M. tuberculosis HigA2 comprises three sections: an N-terminal autocleavage region, an α-helix bundle which contains an HTH motif, and a C-terminal β-lid. The N-terminal region is responsible for toxin binding, but was shown to cleave spontaneously in its absence. The HTH motif performs a key role in DNA binding, with the C-terminal β-lid influencing the interaction by mediating the distance between the motifs. However, M. tuberculosis HigA2 exhibits a unique coordination of the HTH motif and no DNA-binding activity is detected. Three crystal structures of M. tuberculosis HigA2 show a flexible alignment of the HTH motif, which implies that the motif undergoes structural rearrangement to interact with DNA. This study reveals the molecular mechanisms of how transcription factors interact with partner proteins or DNA.http://scripts.iucr.org/cgi-bin/paper?S2052252521007715toxin–antitoxin systemsmycobacterium tuberculosistranscription factorshigbahiga2crystal structurestructure determinationx-ray crystallography |
| spellingShingle | William Richardson Gyun Won Kang Hee Joong Lee Kang Mu Kwon Saron Kim Hyo Jung Kim Chasing the structural diversity of the transcription regulator Mycobacterium tuberculosis HigA2 IUCrJ toxin–antitoxin systems mycobacterium tuberculosis transcription factors higba higa2 crystal structure structure determination x-ray crystallography |
| title | Chasing the structural diversity of the transcription regulator Mycobacterium tuberculosis HigA2 |
| title_full | Chasing the structural diversity of the transcription regulator Mycobacterium tuberculosis HigA2 |
| title_fullStr | Chasing the structural diversity of the transcription regulator Mycobacterium tuberculosis HigA2 |
| title_full_unstemmed | Chasing the structural diversity of the transcription regulator Mycobacterium tuberculosis HigA2 |
| title_short | Chasing the structural diversity of the transcription regulator Mycobacterium tuberculosis HigA2 |
| title_sort | chasing the structural diversity of the transcription regulator mycobacterium tuberculosis higa2 |
| topic | toxin–antitoxin systems mycobacterium tuberculosis transcription factors higba higa2 crystal structure structure determination x-ray crystallography |
| url | http://scripts.iucr.org/cgi-bin/paper?S2052252521007715 |
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