Crystal structures of free and ligand‐bound forms of the TetR/ AcrR‐like</scp> regulator SCO3201 from Streptomyces coelicolor suggest a novel allosteric mechanism - Archive ouverte HAL Access content directly
Journal Articles FEBS Journal Year : 2022

Crystal structures of free and ligand‐bound forms of the TetR/ AcrR‐like regulator SCO3201 from Streptomyces coelicolor suggest a novel allosteric mechanism

(1) , (2, 3) , (3) , (3) , (4)
1
2
3
4

Abstract

TetR/AcrR-like transcription regulators enable bacteria to sense a wide variety of chemical compounds and to dynamically adapt the expression levels of specific genes in response to changing growth conditions. Here, we describe the structural characterisation of SCO3201, an atypical TetR/ AcrR family member from Streptomyces coelicolor that strongly represses antibiotic production and morphological development under conditions of overexpression. We present crystal structures of SCO3201 in its ligand-free state as well as in complex with an unknown inducer, potentially a polyamine. In the ligand-free state, the DNA-binding domains of the SCO3201 dimer are held together in an unusually compact conformation and, as a result, the regulator cannot span the distance between the two half-sites of its operator. Interaction with the ligand coincides with a major structural rearrangement and partial conversion of the so-called hinge helix (a4) to a 3 10-conformation, markedly increasing the distance between the DNAbinding domains. In sharp contrast to what was observed for other TetR/ AcrR-like regulators, the increased interdomain distance might facilitate rather than abrogate interaction of the dimer with the operator. Such a 'reverse' induction mechanism could expand the regulatory repertoire of the TetR/AcrR family and may explain the dramatic impact of SCO3201 overexpression on the ability of S. coelicolor to generate antibiotics and sporulate.
Fichier principal
Vignette du fichier
The FEBS Journal - 2022 - Werten - Crystal structures of free and ligand‐bound forms of the TetR AcrR‐like regulator.pdf (2.55 Mo) Télécharger le fichier
Vignette du fichier
adsct.gif (43 B) Télécharger le fichier
Vignette du fichier
adsct_002.gif (43 B) Télécharger le fichier
Vignette du fichier
CROSSMARK_Color_horizontal.svg (9.67 Ko) Télécharger le fichier
Origin : Publisher files allowed on an open archive
Origin : Files produced by the author(s)

Dates and versions

hal-03857028 , version 1 (25-11-2022)

Identifiers

Cite

Sebastiaan Werten, Paul Waack, Gottfried J Palm, Winfried Hinrichs, Marie-Jöelle Virolle. Crystal structures of free and ligand‐bound forms of the TetR/ AcrR‐like regulator SCO3201 from Streptomyces coelicolor suggest a novel allosteric mechanism. FEBS Journal, 2022, ⟨10.1111/febs.16606⟩. ⟨hal-03857028⟩
0 View
0 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More