DnaK response to expression of protein mutants is dependent on translation rate and stability
Christensen, Signe LU ; Rämisch, Sebastian LU and André, Ingemar LU
(2022)
In Communications Biology
5(1).
- Abstract
Chaperones play a central part in the quality control system in cells by clearing misfolded and aggregated proteins. The chaperone DnaK acts as a sensor for molecular stress by recognising short hydrophobic stretches of misfolded proteins. As the level of unfolded protein is a function of protein stability, we hypothesised that the level of DnaK response upon overexpression of recombinant proteins would be correlated to stability. Using a set of mutants of the λ-repressor with varying thermal stabilities and a fluorescent reporter system, the effect of stability on DnaK response and protein abundance was investigated. Our results demonstrate that the initial DnaK response is largely dependent on protein synthesis rate but as the... (More)
Chaperones play a central part in the quality control system in cells by clearing misfolded and aggregated proteins. The chaperone DnaK acts as a sensor for molecular stress by recognising short hydrophobic stretches of misfolded proteins. As the level of unfolded protein is a function of protein stability, we hypothesised that the level of DnaK response upon overexpression of recombinant proteins would be correlated to stability. Using a set of mutants of the λ-repressor with varying thermal stabilities and a fluorescent reporter system, the effect of stability on DnaK response and protein abundance was investigated. Our results demonstrate that the initial DnaK response is largely dependent on protein synthesis rate but as the recombinantly expressed protein accumulates and homeostasis is approached the response correlates strongly with stability. Furthermore, we observe a large degree of cell-cell variation in protein abundance and DnaK response in more stable proteins.
(Less)
- author
- Christensen, Signe
LU
; Rämisch, Sebastian
LU
and André, Ingemar
LU
- organization
- publishing date
- 2022
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Communications Biology
- volume
- 5
- issue
- 1
- article number
- 597
- publisher
- Nature Publishing Group
- external identifiers
-
- pmid:35710941
- scopus:85132080609
- ISSN
- 2399-3642
- DOI
- 10.1038/s42003-022-03542-2
- language
- English
- LU publication?
- yes
- id
- a9110cfc-6eeb-4294-b00e-416bf1ddf82d
- date added to LUP
- 2022-09-02 14:39:52
- date last changed
- 2024-04-17 13:49:49
@article{a9110cfc-6eeb-4294-b00e-416bf1ddf82d,
abstract = {{<p>Chaperones play a central part in the quality control system in cells by clearing misfolded and aggregated proteins. The chaperone DnaK acts as a sensor for molecular stress by recognising short hydrophobic stretches of misfolded proteins. As the level of unfolded protein is a function of protein stability, we hypothesised that the level of DnaK response upon overexpression of recombinant proteins would be correlated to stability. Using a set of mutants of the λ-repressor with varying thermal stabilities and a fluorescent reporter system, the effect of stability on DnaK response and protein abundance was investigated. Our results demonstrate that the initial DnaK response is largely dependent on protein synthesis rate but as the recombinantly expressed protein accumulates and homeostasis is approached the response correlates strongly with stability. Furthermore, we observe a large degree of cell-cell variation in protein abundance and DnaK response in more stable proteins.</p>}},
author = {{Christensen, Signe and Rämisch, Sebastian and André, Ingemar}},
issn = {{2399-3642}},
language = {{eng}},
number = {{1}},
publisher = {{Nature Publishing Group}},
series = {{Communications Biology}},
title = {{DnaK response to expression of protein mutants is dependent on translation rate and stability}},
url = {{http://dx.doi.org/10.1038/s42003-022-03542-2}},
doi = {{10.1038/s42003-022-03542-2}},
volume = {{5}},
year = {{2022}},
}