8SVZ

Structure of the Francisella response regulator KdpE receiver domain

Summary for 8SVZ

• Entry DOI: 10.2210/pdb8svz/pdb
• Descriptor: Two-component response regulator, BERYLLIUM TRIFLUORIDE ION, MAGNESIUM ION, ... (4 entities in total)
• Functional Keywords: response regulator, transcription regulator, two-component system, transcription
• Biological source: Francisella tularensis subsp. novicida U112
• Total number of polymer chains: 2
• Total formula weight: 29196.06

Authors

Milton, M.E.,Cavanagh, J. (deposition date: 2023-05-17, release date: 2024-06-12)

Primary citation

Gaddy, K.E.,Bensch, E.M.,Cavanagh, J.,Milton, M.E.
Insights into DNA-binding motifs and mechanisms of Francisella tularensis novicida two-component system response regulator proteins QseB, KdpE, and BfpR.
Biochem.Biophys.Res.Commun., 722:150150-150150, 2024

PubMed Abstract: Two component system bacterial response regulators are typically DNA-binding proteins which enable the genetic regulation of many adaptive bacterial behaviors. Despite structural similarity across response regulator families, there is a diverse array of DNA-binding mechanisms. Bacteria usually encode several dozen two-component system response regulators, but Francisella tularensis only encodes three. Due to their simplified response regulatory network, Francisella species are a model for studying the role of response regulator proteins in virulence. Here, we show that Francisella response regulators QseB, KdpE, and BfpR all utilize different DNA-binding mechanisms. Our evidence suggests that QseB follows a simple mechanism whereby it binds a single inverted repeat sequence with a higher affinity upon phosphorylation. This behavior is independent of whether QseB is a positive or negative regulator of the gene as demonstrated by qseB and priM promoter sequences, respectively. Similarly, KdpE binds DNA more tightly upon phosphorylation, but also exhibits a cooperative binding isotherm. While we propose a KdpE binding site, it is possible that KdpE has a complex DNA-binding mechanism potentially involving multiple copies of KdpE being recruited to a promoter region. Finally, we show that BfpR appears to bind a region of its own promoter sequence with a lower affinity upon phosphorylation. Further structural and enzymatic work will need to be performed to deconvolute the KdpE and BfpR binding mechanisms.

PubMed: 38805787
DOI: 10.1016/j.bbrc.2024.150150

Experimental method

X-RAY DIFFRACTION (3.35 Å)