7PT0

SCO3201 with putative ligand

Summary for 7PT0

• Entry DOI: 10.2210/pdb7pt0/pdb
• Related: 4CGR
• Descriptor: TetR family transcriptional regulator, SPERMIDINE (3 entities in total)
• Functional Keywords: transcription, regulator, tetr, dna binding protein
• Biological source: Streptomyces coelicolor
• Total number of polymer chains: 2
• Total formula weight: 46495.89

Authors

Werten, S.,Palm, G.J.,Hinrichs, W. (deposition date: 2021-09-25, release date: 2021-10-20, Last modification date: 2024-02-07)

Primary citation

Werten, S.,Waack, P.,Palm, G.J.,Virolle, M.J.,Hinrichs, W.
Crystal structures of free and ligand-bound forms of the TetR/AcrR-like regulator SCO3201 from Streptomyces coelicolor suggest a novel allosteric mechanism.
Febs J., 290:521-532, 2023

PubMed 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 (α4) to a 3 -conformation, markedly increasing the distance between the DNA-binding 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.

PubMed: 36017630
DOI: 10.1111/febs.16606

Experimental method

X-RAY DIFFRACTION (1.89 Å)