Abstract
The PhoQP two-component system is a signaling complex essential for bacterial virulence and cationic antimicrobial peptide resistance. PhoQ is the histidine kinase chemoreceptor of this tandem machine and assembles in a homodimer conformation spanning the bacterial inner membrane. Currently, a full understanding of the PhoQ signal transduction is hindered by the lack of a complete atomistic structure. In this study, an atomistic model of the key transmembrane (TM) domain is assembled by using molecular simulations, guided by experimental cross-linking data. The formation of a polar pocket involving Asn202 in the lumen of the tetrameric TM bundle is crucial for the assembly and solvation of the domain. Moreover, a concerted displacement of the TM helices at the periplasmic side is found to modulate a rotation at the cytoplasmic end, supporting the transduction of the chemical signal through a combination of scissoring and rotational movement of the TM helices.
Highlights
Two-component systems (TCS) are protein signaling complexes present in most species of bacteria and are used to sense a wide range of environmental stimuli and couple them to adaptive responses [1]
PhoQ is the histidine kinase chemoreceptor of the PhoQ-PhoP tandem machine that detects the concentration of cationic species at the inner membrane of Gram-negative bacteria
By using molecular simulations integrated with cross-linking disulfide scanning data, we present the first structural model of the transmembrane (TM) portion of PhoQ from E. coli
Summary
Two-component systems (TCS) are protein signaling complexes present in most species of bacteria and are used to sense a wide range of environmental stimuli and couple them to adaptive responses [1]. The PhoQP TCS is reported to play a role in the defensive and virulence mechanism for certain Gram-negative bacteria [2,3]. External stimuli, such as the presence of antimicrobial peptides at the periplasmic surface, lead to the autophosphorylation of the PhoQ histidine kinase core, and to the subsequent transfer of the phosphoryl group to the response regulator, which elicits the regulatory response (kinase activity). Apart from the basic understanding of the fundamental signaling mechanism, PhoQP TCS is a promising target for the development of synthetic antimicrobial drugs
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
