7E1L

Crystal structure of apo form PhlH

Summary for 7E1L

• Entry DOI: 10.2210/pdb7e1l/pdb
• Descriptor: DUF1956 domain-containing protein (2 entities in total)
• Functional Keywords: tetr-family regulator, allosteric switching mechanism, biocontrol, transcription
• Biological source: Pseudomonas fluorescens
• Total number of polymer chains: 2
• Total formula weight: 51992.25

Authors

Zhang, N.,Wu, J.,He, Y.X.,Ge, H. (deposition date: 2021-02-01, release date: 2022-02-02, Last modification date: 2024-11-13)

Primary citation

Zhang, N.,Wu, J.,Zhang, S.,Yuan, M.,Xu, H.,Li, J.,Zhang, P.,Wang, M.,Kempher, M.L.,Tao, X.,Zhang, L.Q.,Ge, H.,He, Y.X.
Molecular basis for coordinating secondary metabolite production by bacterial and plant signaling molecules.
J.Biol.Chem., 298:102027-102027, 2022

PubMed Abstract: The production of secondary metabolites is a major mechanism used by beneficial rhizobacteria to antagonize plant pathogens. These bacteria have evolved to coordinate the production of different secondary metabolites due to the heavy metabolic burden imposed by secondary metabolism. However, for most secondary metabolites produced by bacteria, it is not known how their biosynthesis is coordinated. Here, we showed that PhlH from the rhizobacterium Pseudomonas fluorescens is a TetR-family regulator coordinating the expression of enzymes related to the biosynthesis of several secondary metabolites, including 2,4-diacetylphloroglucinol (2,4-DAPG), mupirocin, and pyoverdine. We present structures of PhlH in both its apo form and 2,4-DAPG-bound form and elucidate its ligand-recognizing and allosteric switching mechanisms. Moreover, we found that dissociation of 2,4-DAPG from the ligand-binding domain of PhlH was sufficient to allosterically trigger a pendulum-like movement of the DNA-binding domains within the PhlH dimer, leading to a closed-to-open conformational transition. Finally, molecular dynamics simulations confirmed that two distinct conformational states were stabilized by specific hydrogen bonding interactions and that disruption of these hydrogen bonds had profound effects on the conformational transition. Our findings not only reveal a well-conserved route of allosteric signal transduction in TetR-family regulators but also provide novel mechanistic insights into bacterial metabolic coregulation.

PubMed: 35568198
DOI: 10.1016/j.jbc.2022.102027

Experimental method

X-RAY DIFFRACTION (2.4 Å)