6SRN

Structural basis for control of antibiotic production by bacterial hormones

Summary for 6SRN

• Entry DOI: 10.2210/pdb6srn/pdb
• Descriptor: TetR family transcriptional regulator, 4-(Hydroxymethyl)-2-propylfuran-3-carboxylic acid, GLYCEROL, ... (4 entities in total)
• Functional Keywords: antibiotic, streptomyces, tetr-family transcriptional regulator, signalling, microbial natural product
• Biological source: Streptomyces coelicolor
• Total number of polymer chains: 1
• Total formula weight: 24301.55

Authors

Fulop, V. (deposition date: 2019-09-05, release date: 2020-09-30, Last modification date: 2024-05-15)

Primary citation

Zhou, S.,Bhukya, H.,Malet, N.,Harrison, P.J.,Rea, D.,Belousoff, M.J.,Venugopal, H.,Sydor, P.K.,Styles, K.M.,Song, L.,Cryle, M.J.,Alkhalaf, L.M.,Fulop, V.,Challis, G.L.,Corre, C.
Molecular basis for control of antibiotic production by a bacterial hormone.
Nature, 590:463-467, 2021

PubMed Abstract: Actinobacteria produce numerous antibiotics and other specialized metabolites that have important applications in medicine and agriculture. Diffusible hormones frequently control the production of such metabolites by binding TetR family transcriptional repressors (TFTRs), but the molecular basis for this remains unclear. The production of methylenomycin antibiotics in Streptomyces coelicolor A3(2) is initiated by the binding of 2-alkyl-4-hydroxymethylfuran-3-carboxylic acid (AHFCA) hormones to the TFTR MmfR. Here we report the X-ray crystal structure of an MmfR-AHFCA complex, establishing the structural basis for hormone recognition. We also elucidate the mechanism for DNA release upon hormone binding through the single-particle cryo-electron microscopy structure of an MmfR-operator complex. DNA binding and release assays with MmfR mutants and synthetic AHFCA analogues define the role of individual amino acid residues and hormone functional groups in ligand recognition and DNA release. These findings will facilitate the exploitation of actinobacterial hormones and their associated TFTRs in synthetic biology and in the discovery of new antibiotics.

PubMed: 33536618
DOI: 10.1038/s41586-021-03195-x

Experimental method

X-RAY DIFFRACTION (1.5 Å)