RT Journal Article
SR Electronic
T1 Molecular chaperones inject energy from ATP hydrolysis into the non-equilibrium stabilisation of native proteins
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 146852
DO 10.1101/146852
A1 Pierre Goloubinoff
A1 Alberto S. Sassi
A1 Bruno Fauvet
A1 Alessandro Barducci
A1 Paolo De Los Rios
YR 2017
UL http://biorxiv.org/content/early/2017/06/07/146852.abstract
AB Protein homeostasis, namely the ensemble of cellular mechanisms collectively controlling the activity, stability and conformational states of proteins, depends on energy-consuming processes. De novo protein synthesis requires ATP hydrolysis for peptide bond formation. Controlled degradation by the chaperone-gated proteases requires ATP hydrolysis to unfold target proteins and render their peptide bonds accessible to hydrolysis. During and following translation, different classes of molecular chaperones require ATP hydrolysis to control the conformational state of proteins, favor their folding into their active conformation and avoid, under stress, their conversion into potentially harmful aggregates. Furthermore, specific ATP-fueled unfolding chaperones can dynamically revert aggregation itself. We used here various biochemical assays and physical modeling to show that both bacterial chaperones GroEL (HSP60) and DnaK (HSP70) can use the energy liberated by ATP hydrolysis to maintain proteins in their active state even under conditions that do not favor, thermodynamically, the native state. The energy from ATP hydrolysis is thus injected by the chaperones in the system and converted into an enhanced, non-equilibrium steady-state stabilization of the native state of their substrates. Upon ATP consumption, the chaperone substrates spontaneously revert to their equilibrium non-native state.