Abstract
The signal recognition particle (SRP), which mediates cotranslational protein targeting to cellular membranes, is universally conserved and essential for bacterial and mammalian cells. However, the current understanding of the role of SRP in cell physiology and pathology is still poor, and the reasons behind its essential role in cell survival remain unclear. Here, we systematically analyzed the consequences of SRP loss in E. coli using time-resolved quantitative proteomic analyses. A series of snapshots of the steady-state and newly synthesized proteome unveiled three stages of cellular responses to SRP depletion, and demonstrated essential roles of SRP in metabolism, membrane potential, and protein and energy homeostasis in both the membrane and cytoplasm. We also identified a group of periplasmic proteins, including key molecular chaperones, whose localization was impaired by the loss of SRP; this and additional results showed that SRP is crucial for protein homeostasis in the bacterial envelope. These results reveal the extensive roles that SRP plays in bacterial physiology, emphasize the importance of proper membrane protein biogenesis, and demonstrate the ability of time-resolved quantitative proteomic analysis to provide new biological insights.
Highlights
Previous work showed that SRP depletion causes only a mild kinetic defect in the localization of inner membrane proteins [7, 8, 11, 12]; we found here that the steady-state level or distribution of most inner membrane proteins was not significantly altered by SRP depletion
The numerous cellular stress responses upon the loss of SRP observed here indicate stress and compromised integrity of the membrane. These observations led us to speculate that cotranslational protein targeting by the SRP is important for the localization of inner membrane proteins, and for their proper folding, integration, or assembly
The immediate reduction of pmf upon SRP depletion suggests that such folding/assembly defects occurred as a direct consequence of the loss of SRP
Summary
Rious consequences of SRP depletion may cause cell death. These include the collapse in metabolism and membrane potential, defects in envelope integrity, and genome instability. The results here and from previous work present two opposing sets of observations.
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.
