Novel proteomic tools reveal essential roles of SRP and importance of proper membrane protein biogenesis.
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.
Division of Chemistry and Chemical Engineering, Beckman Institute, California Institute of Technology, Pasadena, California 91125, USA. zhangd@caltech.edu
Dawei
D
Zhang
Michael J
MJ
Sweredoski
Robert L J
RL
Graham
Sonja
S
Hess
Shu-ou
SO
Shan
D002463:Cell Membrane Permeability; D002465:Cell Movement; D002853:Chromatography, Liquid; D003593:Cytoplasm / Q000378:metabolism; D004926:Escherichia coli / Q000254:growth & development / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000378:metabolism*; D008564:Membrane Potentials; D008565:Membrane Proteins / Q000378:metabolism*; D001678:Organelle Biogenesis; D021381:Protein Transport; D020543:Proteome / Q000032:analysis*; D040901:Proteomics; D012270:Ribosomes / Q000378:metabolism; D018271:Signal Recognition Particle / Q000235:genetics / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013347:Subcellular Fractions
D029968:Escherichia coli Proteins; D008565:Membrane Proteins; D020543:Proteome; D018271:Signal Recognition Particle