Sci. Adv. 2, e1601625 (2016)

Credit: AAAS

Chaperones have key roles in promoting protein folding events. In the energy landscape theory of protein folding, chaperones mitigate the 'frustration' and increased dynamics that arise from the drive to minimize interaction free energy within the context of a protein sequence. To better understand the mechanistic principles involved in client interaction as well as a chaperone's influence on client dynamics and native structure, He et al. used NMR spectroscopy to examine the atomic-level interactions between the ATP-dependent bacterial chaperone Spy and its client Im7 in a partially folded as well as in an unfolded state. Their data are consistent with a model in which Spy acts as a passive interaction surface, exhibiting minimal structural changes while binding to regions of Im7 with increased local flexibility and high local frustration levels, but leaving the Im7 backbone essentially intact. Binding of the frustrated regions by Spy is associated with increases in dynamics and internal motion within Im7. Studies of two additional chaperones gave similar results, suggesting that the recognition of frustrated segments that leads to increased dynamics and the opportunity this creates for the client protein to search available conformations are fundamental features of chaperone function.