Structural insights into the functional divergence of WhiB-like proteins in Mycobacterium tuberculosis.
Mol Cell
; 81(14): 2887-2900.e5, 2021 07 15.
Article
en En
| MEDLINE
| ID: mdl-34171298
ABSTRACT
WhiB7 represents a distinct subclass of transcription factors in the WhiB-Like (Wbl) family, a unique group of iron-sulfur (4Fe-4S] cluster-containing proteins exclusive to the phylum of Actinobacteria. In Mycobacterium tuberculosis (Mtb), WhiB7 interacts with domain 4 of the primary sigma factor (σA4) in the RNA polymerase holoenzyme and activates genes involved in multiple drug resistance and redox homeostasis. Here, we report crystal structures of the WhiB7σA4 complex alone and bound to its target promoter DNA at 1.55-Å and 2.6-Å resolution, respectively. These structures show how WhiB7 regulates gene expression by interacting with both σA4 and the AT-rich sequence upstream of the -35 promoter DNA via its C-terminal DNA-binding motif, the AT-hook. By combining comparative structural analysis of the two high-resolution σA4-bound Wbl structures with molecular and biochemical approaches, we identify the structural basis of the functional divergence between the two distinct subclasses of Wbl proteins in Mtb.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Proteínas Bacterianas
/
Factores de Transcripción
/
Proteínas Hierro-Azufre
/
Mycobacterium tuberculosis
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Mol Cell
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2021
Tipo del documento:
Article
País de afiliación:
Estados Unidos