# Thermodynamic bounds on the ultra- and infra-affinity of Hsp70 for its substrates

## TL;DR

This paper establishes thermodynamic limits on the ultra- and infra-affinity of Hsp70 proteins for their substrates, highlighting the role of ATP hydrolysis and cofactors in modulating binding strength beyond equilibrium.

## Contribution

It introduces thermodynamic bounds for Hsp70's ultra-affinity and demonstrates how reaction schemes can modulate affinity levels, including infra-affinity, through non-equilibrium processes.

## Key findings

- Cofactors are essential for ultra-affinity beyond equilibrium.
- Reaction schemes can modulate affinity to be stronger or weaker.
- Thermodynamic bounds define limits of Hsp70 substrate binding.

## Abstract

The 70 kDa Heat Shock Proteins Hsp70 have several essential functions in living systems, such as protecting cells against protein aggregation, assisting protein folding, remodeling protein complexes and driving the translocation into organelles. These functions require high affinity for non-specific amino-acid sequences that are ubiquitous in proteins. It has been recently shown that this high affinity, called ultra-affinity, depends on a process driven out of equilibrium by ATP hydrolysis. Here we establish the thermodynamic bounds for ultra-affinity, and further show that the same reaction scheme can in principle be used both to strengthen and to weaken affinities (leading in this case to infra-affinity). We show that cofactors are essential to achieve affinity beyond the equilibrium range. Finally, biological implications are discussed.