Thermodynamics of protein destabilization in live cells.

Research output: Contribution to journalArticle

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.

Details

Authors
  • Jens Danielsson
  • Xin Mu
  • Lisa Lang
  • Huabing Wang
  • Andres Binolfi
  • François-Xavier Theillet
  • Beata Bekei
  • Derek Logan
  • Philipp Selenko
  • Håkan Wennerström
  • Mikael Oliveberg
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Structural Biology
Original languageEnglish
Pages (from-to)12402-12407
JournalProceedings of the National Academy of Sciences
Volume112
Issue number40
Publication statusPublished - 2015
Publication categoryResearch
Peer-reviewedYes