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| Status |
Public on Jul 20, 2022 |
| Title |
System-wide analyses reveal essential roles of N-terminal protein modification in bacterial physiology |
| Organism |
Escherichia coli |
| Experiment type |
Other
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| Summary |
Removal of the N-terminal formyl group on nascent proteins by peptide deformylase (PDF) is the most prevalent protein modification in bacteria that impacts over 90% of the proteome. PDF is essential and a critical target of antibiotic development; however, its role in bacterial physiology remains a long-standing question. In this work, we used system-wide and time-resolved analyses of the E. coli translatome and proteome to investigate the consequences of PDF inhibition at different stages. We found that PDF inhibition results in the rapid activation of cellular stress responses, especially those associated with defects in protein folding and perturbations at the bacterial inner membrane, followed by a global downregulation of metabolic pathways. Functional assays reveal the rapid hyperpolarization of the plasma membrane and impaired membrane integrity upon PDF inhibition, suggesting that disruption of plasma membrane is the most immediate and primary consequence of formyl group retention on nascent proteins. Our work resolves the physiological function of a ubiquitous N-terminal protein modification and uncovers its crucial role in maintaining the proper structure and function of the bacterial membrane.
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| Overall design |
Investigating the change in translatome upon inhibition of PDF by actinonin (ACT) treatment.
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| Contributor(s) |
Yang C, Zhu Z, Shan S |
| Citation(s) |
35942092 |
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| Submission date |
Mar 24, 2022 |
| Last update date |
Aug 24, 2022 |
| Contact name |
Zikun Zhu |
| E-mail(s) |
zzhu@caltech.edu
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| Organization name |
California Institute of Technology
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| Department |
CCE
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| Lab |
Shan
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| Street address |
1200 E California Blvd
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| City |
Pasadena |
| State/province |
CA |
| ZIP/Postal code |
91125 |
| Country |
USA |
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| Platforms (2) |
| GPL18133 |
Illumina HiSeq 2500 (Escherichia coli) |
| GPL32081 |
NextSeq 2000 (Escherichia coli) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA819450 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE199360_RAW.tar |
24.0 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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