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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 ; 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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Contribution to journal
publication status
published
subject
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Proceedings of the National Academy of Sciences
volume
112
issue
40
pages
12402 - 12407
publisher
National Acad Sciences
external identifiers
  • pmid:26392565
  • wos:000363125400053
  • scopus:84943392880
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
2015-10-30 13:10:45
date last changed
2017-10-29 03:10:52
@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 Acad 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},
  volume       = {112},
  year         = {2015},
}