Molecular biology: Mature proteins braced by a chaperone.

Abstract

Hsp70 chaperone molecules help other proteins to fold, and were thought to bind mainly to unfolded proteins. Single-molecule experiments now suggest that Hsp70s can also stabilize almost fully folded proteins. See Letter p.448 The protein-chaperone system centred on Hsp70 performs a variety of cellular control tasks, including folding assistance, protection against aggregation, trafficking and regulation of enzyme activity, a versatility that has been hard to reconcile with structural data, which suggest that Hsp70 only binds extended polypeptide segments. Now, using laser molecular tweezers, Sander Tans and colleagues show that the bacterial homolog of Hsp70, known as DnaK, relies on its 'groove' to bind unfolded proteins, but can also bind folded structures, thanks to its 'lid', with control of ATP hydrolysis by co-chaperones allowing regulation of such contrasting effects. Contrary to known stabilization mechanisms, through precise structural fit, Hsp70 can stabilize a vast repertoire of client proteins, through a clamp-like, ATP-driven conformational change.