Thermodynamics of protein destabilization in live cells.

JENS DANIELSSON; XIAN MU; LISA LANG; HAU WANG; ANDRÉS BINOLFI; FRANCOIS-XAVIER THEILLET; BEATA BEKEI ; DEREK LOGAN; PHILIPP SELENKO; H WENNERSTRÖM; MIKAEL OLIVEBERG

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

NATL ACAD SCIENCES

Lugar: Washington DC, USA; Año: 2015

0027-8424

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.