Mechanism of outer membrane destabilization by global reduction of protein content
Abstract/Contents
- Abstract
- The outer membrane (OM) of Gram-negative bacteria such as Escherichia coli is an asymmetric bilayer with the glycolipid lipopolysaccharide (LPS) in the outer leaflet and glycerophospholipids in the inner. Nearly all integral OM proteins (OMPs) have a characteristic beta-barrel fold and are assembled in the OM by the BAM complex, which contains one essential -barrel protein (BamA), one essential lipoprotein (BamD), and three non-essential lipoproteins (BamBCE). A gain-of-function mutation in bamA enables survival in the absence of BamD, showing that the essential function of this protein is regulatory. We demonstrate that the global reduction in OMPs caused by BamD loss weakens the OM, altering cell shape and causing OM rupture in spent medium. To fill the void created by OMP loss, PLs flip into the outer leaflet. Under these conditions, mechanisms that remove PLs from the outer leaflet create tension between the OM leaflets, which contributes to membrane rupture. Rupture is prevented by suppressor mutations that release the tension by halting PL removal from the outer leaflet. However, these suppressors do not restore OM stiffness or normal cell shape, revealing a possible connection between OM stiffness and cell shape.
Description
| Type of resource | mixed material, Dataset, still image |
|---|---|
| Publication date | June 1, 2023 |
Creators/Contributors
| Author | Mikheyeva, Irina V. | |
|---|---|---|
| Author | Sun, Jiawei | |
| Author | Huang, Kerwyn Casey | |
| Author | Silhavy, Thomas J. |
Subjects
| Subject | bamD |
|---|---|
| Subject | outer membrane |
| Subject | outer membrane proteins |
| Subject | phospholipid flow |
| Subject | pldA |
| Subject | lpxC |
| Subject | mlaA |
| Genre | Mixed materials |
| Genre | Data |
| Genre | Image |
| Genre | Software/code |
| Genre | Data sets |
| Genre | Dataset |
Bibliographic information
| Related item |
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|---|---|
| DOI | https://doi.org/10.25740/gp172gf6221 |
| Location | https://purl.stanford.edu/gp172gf6221 |
Access conditions
- Use and reproduction
- User agrees that, where applicable, content will not be used to identify or to otherwise infringe the privacy or confidentiality rights of individuals. Content distributed via the Stanford Digital Repository may be subject to additional license and use restrictions applied by the depositor.
- License
- This work is licensed under a Creative Commons Attribution 4.0 International license (CC BY).
Preferred citation
- Preferred citation
- Mikheyeva, I., Sun, J., Huang, K., and Silhavy, T. (2023). Mechanism of outer membrane destabilization by global reduction of protein content. Stanford Digital Repository. Available at https://purl.stanford.edu/gp172gf6221. https://doi.org/10.25740/gp172gf6221.
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Stanford Research Data
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