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Thermodynamics of protein destabilization in live cells.

Danielsson, Jens ; Mu, Xin ; Lang, Lisa ; Wang, Huabing ; Binolfi, Andres ; Theillet, François-Xavier ; Bekei, Beata ; Logan, Derek LU orcid ; Selenko, Philipp and Wennerström, Håkan LU , et al. (2015) In Proceedings of the National Academy of Sciences 112(40). p.12402-12407
Abstract
Although protein folding and stability have been well explored under simplified conditions in vitro, it is yet unclear how these basic self-organization events are modulated by the crowded interior of live cells. To find out, we use here in-cell NMR to follow at atomic resolution the thermal unfolding of a β-barrel protein inside mammalian and bacterial cells. Challenging the view from in vitro crowding effects, we find that the cells destabilize the protein at 37 °C but with a conspicuous twist: While the melting temperature goes down the cold unfolding moves into the physiological regime, coupled to an augmented heat-capacity change. The effect seems induced by transient, sequence-specific, interactions with the cellular components,... (More)
Although protein folding and stability have been well explored under simplified conditions in vitro, it is yet unclear how these basic self-organization events are modulated by the crowded interior of live cells. To find out, we use here in-cell NMR to follow at atomic resolution the thermal unfolding of a β-barrel protein inside mammalian and bacterial cells. Challenging the view from in vitro crowding effects, we find that the cells destabilize the protein at 37 °C but with a conspicuous twist: While the melting temperature goes down the cold unfolding moves into the physiological regime, coupled to an augmented heat-capacity change. The effect seems induced by transient, sequence-specific, interactions with the cellular components, acting preferentially on the unfolded ensemble. This points to a model where the in vivo influence on protein behavior is case specific, determined by the individual protein's interplay with the functionally optimized "interaction landscape" of the cellular interior. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Proceedings of the National Academy of Sciences
volume
112
issue
40
pages
12402 - 12407
publisher
National Academy of Sciences
external identifiers
  • pmid:26392565
  • wos:000363125400053
  • scopus:84943392880
  • pmid:26392565
ISSN
1091-6490
DOI
10.1073/pnas.1511308112
language
English
LU publication?
yes
id
833c84d5-59d3-4742-8310-63d6701be629 (old id 8035396)
date added to LUP
2016-04-01 10:25:41
date last changed
2022-04-27 21:51:56
@article{833c84d5-59d3-4742-8310-63d6701be629,
  abstract     = {{Although protein folding and stability have been well explored under simplified conditions in vitro, it is yet unclear how these basic self-organization events are modulated by the crowded interior of live cells. To find out, we use here in-cell NMR to follow at atomic resolution the thermal unfolding of a β-barrel protein inside mammalian and bacterial cells. Challenging the view from in vitro crowding effects, we find that the cells destabilize the protein at 37 °C but with a conspicuous twist: While the melting temperature goes down the cold unfolding moves into the physiological regime, coupled to an augmented heat-capacity change. The effect seems induced by transient, sequence-specific, interactions with the cellular components, acting preferentially on the unfolded ensemble. This points to a model where the in vivo influence on protein behavior is case specific, determined by the individual protein's interplay with the functionally optimized "interaction landscape" of the cellular interior.}},
  author       = {{Danielsson, Jens and Mu, Xin and Lang, Lisa and Wang, Huabing and Binolfi, Andres and Theillet, François-Xavier and Bekei, Beata and Logan, Derek and Selenko, Philipp and Wennerström, Håkan and Oliveberg, Mikael}},
  issn         = {{1091-6490}},
  language     = {{eng}},
  number       = {{40}},
  pages        = {{12402--12407}},
  publisher    = {{National Academy of Sciences}},
  series       = {{Proceedings of the National Academy of Sciences}},
  title        = {{Thermodynamics of protein destabilization in live cells.}},
  url          = {{http://dx.doi.org/10.1073/pnas.1511308112}},
  doi          = {{10.1073/pnas.1511308112}},
  volume       = {{112}},
  year         = {{2015}},
}