Cage folding

A well-designed chaperone cage helps proteins to fold quickly, say Yun-Chi Tang, F. Ulrich Hartl, Manajit Hayer-Hartl, and colleagues (Max Planck Institute of Biochemistry, Martinsried, Germany), probably by limiting the number of possible folding intermediates.

Bacteria's most well-studied chaperone is the GroEL nano-cage, which encapsulates a folding substrate within its walls. This cage was thought to be little more than a way to isolate substrates to prevent aggregation of slow-folding proteins. But the new findings suggest an active role, as folding rates inside the cage were up to 15-fold faster than in solution.

Folding is hastened by several cage features, including cage size. For small proteins, GroEL mutants with a smaller cavity further accelerated folding, until a point at which necessary rearrangements were spatially restricted. Confinement hastens folding by preventing...