Chasing the structural diversity of the transcription regulator Mycobacterium tuberculosis HigA2.
William RichardsonGyun Won KangHee Joong LeeKang Mu KwonSaron KimHyo Jung KimPublished in: IUCrJ (2021)
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.
Keyphrases
- dna binding
- transcription factor
- mycobacterium tuberculosis
- circulating tumor
- cell free
- pulmonary tuberculosis
- single molecule
- gene expression
- escherichia coli
- nucleic acid
- hiv aids
- circulating tumor cells
- dna methylation
- emergency department
- heat shock
- electronic health record
- heat stress
- human immunodeficiency virus
- hepatitis c virus
- antiretroviral therapy
- hiv infected