Thermodynamics of protein destabilization in live cells.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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.

Detaljer

Författare
  • Jens Danielsson
  • Xin Mu
  • Lisa Lang
  • Huabing Wang
  • Andres Binolfi
  • François-Xavier Theillet
  • Beata Bekei
  • Derek Logan
  • Philipp Selenko
  • Håkan Wennerström
  • Mikael Oliveberg
Enheter & grupper
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Strukturbiologi
Originalspråkengelska
Sidor (från-till)12402-12407
TidskriftProceedings of the National Academy of Sciences
Volym112
Utgivningsnummer40
StatusPublished - 2015
PublikationskategoriForskning
Peer review utfördJa