Proteins that switch folds.

An increasing number of proteins demonstrate the ability to switch between very different fold topologies, expanding their functional utility through new binding interactions. Recent examples of fold switching from naturally occurring and designed systems have a number of common features: (i) The structural transitions require states with diminished stability; (ii) Switching involves flexible regions in one conformer or the other; (iii) A new binding surface is revealed in the alternate fold that can lead to both stabilization of the alternative state and expansion of biological function. Fold switching not only provides insight into how new folds evolve, but also indicates that an amino acid sequence has more information content than previously thought. A polypeptide chain can encode a stable fold while simultaneously hiding latent propensities for alternative states with novel functions. Copyright (c) 2010 Elsevier Ltd. All rights reserved.