 Heat shock proteins of 70 kilodaltons, HSP70S, are ubiquitous molecular chaperones that regulate the folding of proteins and other essential cellular functions. A new study suggests that these proteins can be divided into three distinct states, each with different properties. The first state, called R, restricts ATP hydrolysis and does not bind peptids. The second state, called S, allows for rapid ATP hydrolysis and has high intrinsic substrate affinity, but also has fast binding kinetics. Finally, the third state, called U, binds peptids tightly, but with slow kinetics of exchange. This model explains how heat shock proteins can regulate their activity by switching between these states. This article was authored by Wayne A. Hendrickson.