2025 Hyper Recent •CC0 1.0 Universal

This work is dedicated to the public domain. No rights reserved.

Access Preprint From Server
April 12th, 2025
Version: 1
University of Maryland, Baltimore County
biochemistry
biorxiv

The Response Regulator BqsR/CarR Controls Ferrous Iron (Fe2+) Acquisition in Pseudomonas aeruginosa

Paredes, A.Open in Google Scholar•Singh, H.Open in Google Scholar•Hull, M. T.Open in Google Scholar•Greene, D.Open in Google Scholar•Northrup, A. J.Open in Google Scholar•Brown, J. B.Open in Google Scholar•Chacon, K. N.Open in Google Scholar•Patrauchan, M. A.Open in Google Scholar•Smith, A. T.Open in Google Scholar

Pseudomonas aeruginosa is a ubiquitous, Gram-negative bacterium that forms biofilms and is responsible for antibiotic-resistant nosocomial infections in humans. The P. aeruginosa BqsRS two-component system (TCS) regulates biofilm formation and dispersal by sensing extracytoplasmic Fe2+, but the mechanistic details of this process are poorly understood. In this work, we report the crystal and solution structures of the PaBqsR response regulator (RR) receiver domain (RD), comprising a ({beta})5 response regulator assembly, and DNA-binding domain (DBD), comprising a winged helix-turn-helix motif. Consistent with its cognate stimulus being Fe2+, we show that PaBqsR binds directly to the promoter region of the feo operon that encodes the bacterial Fe2+ transport system Feo. Transcriptional studies show that PaBqsR is a global regulator that negatively controls the feo operon, and deletion of bqsR provides a growth advantage of PAO1 in the presence of Fe2+ as its only iron source. Surprisingly, X-ray absorption spectroscopy (XAS) shows that recombinant PaBqsR binds a single Fe2+ ion in a His-rich site, divergent from other members of the OmpR-like family. These exciting results reveal that the BqsRS system controls Fe2+ acquisition in P. aeruginosa and suggest that this system may be an attractive future therapeutic target to treat nosocomial infections.

Similar Papers

biorxiv
Tue Apr 15 2025
An intrinsically disordered region mediates RNA-binding selectivity and pro-oncogenic activities of LARP6
Intrinsically disordered regions (IDRs) are prevalent in RNA-binding proteins (RBPs), yet their roles in RNA interactions remain poorly defined. Here, we examined the structured and disordered RNA-binding activities of LARP6, an RBP with a diverse RNA-binding repertoire. Using mass spectrometry-based RNA interaction mapping in living cells, we identified direct LARP6-RNA contacts within both the s...
Capraro, F.
•
Abis, G.
•
Incocciati, A.
•
Karimzadeh, M.
...•
Mardakheh, F. K.
biorxiv
Mon Apr 14 2025
Designed NGF mimetics with reduced nociceptive signatures in neurons
The clinical use of Nerve Growth Factor (NGF) for neuronal regeneration has been hampered by pain sensitization side effects. NGF signals through the receptor tyrosine kinase TrkA and the co-receptor p75NTR; pain sensitization is thought to involve p75NTR. We sought to overcome this limitation by de novo design of a TrkA agonist that does not bind p75NTR. We designed homodimeric TrkA engaging cons...
Schlichthaerle, T.
•
Yang, A.
•
Detraux, D.
•
Johnson, D. E.
...•
Baker, D.
biorxiv
Mon Apr 14 2025
Catalytic Mechanism and Differential Alarmone Regulation of a Conserved Stringent Nucleosidase
Understanding how bacteria rapidly adapt their metabolism in response to external stimuli is key to addressing the present crisis of antibiotics-resistant infections. In the Gram-negative bacterium Escherichia coli, the universal stringent response is elicited in response to some antibiotics and involves production of the global alarmones, (p)ppGpp, which bind directly to many cellular targets. Th...
Barentsen, R.
•
Kronborg, K.
•
Brodersen, D. E.
•
ZHANG, Y. E.
biorxiv
Mon Apr 14 2025
Single-Molecule Kinetic Exploration of Functional Substates in an Evolving Phosphotriesterase
Enzymes achieve catalysis by dynamically sampling diverse conformational states. Beyond this plasticity, individual enzyme molecules occupy metastable substates, forming an ensemble of functional substates within a population. Since shifts in functional substate dynamics drive phenotypic variation, their evolutionary trajectories are central to the emergence of new functions. However, the challeng...
Sakuma, M.
•
Mahato, D. R.
•
Feixas, F.
•
Jackson, C. J.
...•
Tokuriki, N.
biorxiv
Mon Apr 14 2025
Genetic variants linked to neurodevelopmental disorders within the β3-β4 loop of the TRIO PH2 domain release autoinhibition of GEF2 activity.
The TRIO protein contains two guanine exchange factor (GEF) domains, GEF1 and GEF2, which coordinate cytoskeletal rearrangements by activating Rho family GTPases. Rare variants that impact TRIO GEF1 function are associated with autism spectrum disorder, developmental delay, and intellectual disability, but variants are also found throughout the gene. GEF1 promotes GTP exchange on Rac1 and RhoG, wh...
Carrizales, M. G.
•
Boulton, A.
•
Koleske, A. J.
biorxiv
Mon Apr 14 2025
A structural basis for chaperone repression of stress signalling from the endoplasmic reticulum
The endoplasmic reticulum (ER) unfolded protein response (UPR) is tuned by the balance between unfolded proteins and chaperones. While reserve chaperones are known to suppress the UPR transducers via their stress-sensing luminal domains, the underlying structural mechanisms remain unclear. Cellular and biophysical analyses established that the ER chaperone AGR2 forms a repressive complex with the ...
Neidhardt, L.
•
Tung, J.
•
Kuchersky, M.
•
Milczarek, J.
...•
Yan, Y.
biorxiv
Mon Apr 14 2025
Preliminary characterization of CbcS from Geobacter sulfurreducens ' Cbc4 complex: a putative novel respiratory pathway
Electroactive bacteria mediate electron exchange with external surfaces through a process known as extracellular electron transfer (EET). A key step in EET is the transfer of electrons from the menaquinone pool to inner membrane-associated quinone-cytochrome c oxidoreductase complexes, which subsequently relay electrons to periplasmic redox partners. Gene knockout and proteomic analyses have ident...
Fernandes, M. V.
•
Antunes, J. M. A.
•
Salgueiro, C. A.
•
Morgado, L.
biorxiv
Sat Apr 12 2025
GLUT4 translocation with insulin: revisiting the case for dose-dependent quantal release
In mammalian fat and muscle cells, insulin stimulates the translocation of the glucose transporter GLUT4 from intracellular storage compartments to the plasma membrane in adipocytes and muscle cells, significantly increasing glucose uptake. In unstimulated (basal) cells, GLUT4 is sequestered in non-cycling/very slowly cycling compartments. Insulin mobilizes GLUT4 by releasing it from sequestration...
Romenskaia, I.
•
Mastick, C. C.
•
Coster, A.
biorxiv
Sat Apr 12 2025
An analysis of free energy methods to quantify and displace the KRasG12D Thr58 water
The KRasG12D mutant is an attractive target in oncology and can now be drugged via the switch-II allosteric pocket. Non-covalent ligands typically bind in the presence of a conserved structural water, which interacts with Thr58 and Gly10. In this work, we use a dataset of published non-covalent KRasG12D inhibitors to evaluate free energy methods for the interaction with or displacement of this con...
Dickson, C. J.
biorxiv
Sat Apr 12 2025
The proofreading mechanism of the human leading strand DNA polymerase ϵ holoenzyme
The eukaryotic leading strand DNA polymerase epsilon is a dual function enzyme with a proofreading exonuclease site located 40 angstroms from the DNA synthesizing polymerase site. Errors in Pol epsilon proofreading can cause various mutations, including C to G transversions, the most prevalent mutation in cancers and genetic diseases. Pol epsilon interacts with all three subunits of the PCNA ring ...
Wang, F.
•
He, Q.
•
O'Donnell, M. E.
•
Li, H.