Hsp70 chaperones are non-equilibrium machines that achieve ultra-affinity by energy consumption

Elife. 2014 May 27;3:e02218. doi: 10.7554/eLife.02218.


70-kDa Heat shock proteins are ATP-driven molecular chaperones that perform a myriad of essential cellular tasks. Although structural and biochemical studies have shed some light on their functional mechanism, the fundamental issue of the role of energy consumption, due to ATP-hydrolysis, has remained unaddressed. Here we establish a clear connection between the non-equilibrium nature of Hsp70, due to ATP hydrolysis, and the determining feature of its function, namely its high affinity for its substrates. Energy consumption can indeed decrease the dissociation constant of the chaperone-substrate complex by several orders of magnitude with respect to an equilibrium scenario. We find that the biochemical requirements for observing such ultra-affinity coincide with the physiological conditions in the cell. Our results rationalize several experimental observations and pave the way for further analysis of non-equilibrium effects underlying chaperone functions.DOI: http://dx.doi.org/10.7554/eLife.02218.001.

Keywords: chaperones; dissociation constant; non-equilibrium.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • HSP70 Heat-Shock Proteins / physiology*
  • Hydrolysis
  • Models, Chemical
  • Molecular Chaperones / physiology*


  • HSP70 Heat-Shock Proteins
  • Molecular Chaperones
  • Adenosine Triphosphate

Grant support

The funder had no role in study design, data collection and interpretation, or the decision to submit the work for publication.