System-wide analyses reveal essential roles of N-terminal protein modification in bacterial membrane integrity
Summary: The removal of the N-terminal formyl group on nascent proteins by peptide deformylase (PDF) is the most prevalent protein modification in bacteria. PDF is a critical target of antibiotic development; however, its role in bacterial physiology remains a long-standing question. This work used...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-08-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004222010288 |
| _version_ | 1828372272979640320 |
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| author | Chien-I Yang Zikun Zhu Jeffrey J. Jones Brett Lomenick Tsui-Fen Chou Shu-ou Shan |
| author_facet | Chien-I Yang Zikun Zhu Jeffrey J. Jones Brett Lomenick Tsui-Fen Chou Shu-ou Shan |
| author_sort | Chien-I Yang |
| collection | DOAJ |
| description | Summary: The removal of the N-terminal formyl group on nascent proteins by peptide deformylase (PDF) is the most prevalent protein modification in bacteria. PDF is a critical target of antibiotic development; however, its role in bacterial physiology remains a long-standing question. This work used the time-resolved analyses of the Escherichia coli translatome and proteome to investigate the consequences of PDF inhibition. Loss of PDF activity rapidly induces cellular stress responses, especially those associated with protein misfolding and membrane defects, followed by a global down-regulation of metabolic pathways. Rapid membrane hyperpolarization and impaired membrane integrity were observed shortly after PDF inhibition, suggesting that the plasma membrane disruption is the most immediate and primary consequence of formyl group retention on nascent proteins. This work resolves the physiological function of a ubiquitous protein modification and uncovers its crucial role in maintaining the structure and function of the bacterial membrane. |
| first_indexed | 2024-04-14T07:01:39Z |
| format | Article |
| id | doaj.art-b29a3f98361f4d22bc538b3bcbf10a0b |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-14T07:01:39Z |
| publishDate | 2022-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-b29a3f98361f4d22bc538b3bcbf10a0b2022-12-22T02:06:44ZengElsevieriScience2589-00422022-08-01258104756System-wide analyses reveal essential roles of N-terminal protein modification in bacterial membrane integrityChien-I Yang0Zikun Zhu1Jeffrey J. Jones2Brett Lomenick3Tsui-Fen Chou4Shu-ou Shan5Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA, USADivision of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA, USAProteome Exploration Laboratory, Beckman Institute, California Institute of Technology, Pasadena, CA, USAProteome Exploration Laboratory, Beckman Institute, California Institute of Technology, Pasadena, CA, USAProteome Exploration Laboratory, Beckman Institute, California Institute of Technology, Pasadena, CA, USADivision of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA, USA; Corresponding authorSummary: The removal of the N-terminal formyl group on nascent proteins by peptide deformylase (PDF) is the most prevalent protein modification in bacteria. PDF is a critical target of antibiotic development; however, its role in bacterial physiology remains a long-standing question. This work used the time-resolved analyses of the Escherichia coli translatome and proteome to investigate the consequences of PDF inhibition. Loss of PDF activity rapidly induces cellular stress responses, especially those associated with protein misfolding and membrane defects, followed by a global down-regulation of metabolic pathways. Rapid membrane hyperpolarization and impaired membrane integrity were observed shortly after PDF inhibition, suggesting that the plasma membrane disruption is the most immediate and primary consequence of formyl group retention on nascent proteins. This work resolves the physiological function of a ubiquitous protein modification and uncovers its crucial role in maintaining the structure and function of the bacterial membrane.http://www.sciencedirect.com/science/article/pii/S2589004222010288Molecular biologyBacteriologyOmics |
| spellingShingle | Chien-I Yang Zikun Zhu Jeffrey J. Jones Brett Lomenick Tsui-Fen Chou Shu-ou Shan System-wide analyses reveal essential roles of N-terminal protein modification in bacterial membrane integrity iScience Molecular biology Bacteriology Omics |
| title | System-wide analyses reveal essential roles of N-terminal protein modification in bacterial membrane integrity |
| title_full | System-wide analyses reveal essential roles of N-terminal protein modification in bacterial membrane integrity |
| title_fullStr | System-wide analyses reveal essential roles of N-terminal protein modification in bacterial membrane integrity |
| title_full_unstemmed | System-wide analyses reveal essential roles of N-terminal protein modification in bacterial membrane integrity |
| title_short | System-wide analyses reveal essential roles of N-terminal protein modification in bacterial membrane integrity |
| title_sort | system wide analyses reveal essential roles of n terminal protein modification in bacterial membrane integrity |
| topic | Molecular biology Bacteriology Omics |
| url | http://www.sciencedirect.com/science/article/pii/S2589004222010288 |
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