Some proteins do not fold fully until they meet their functional partners. Folding in concert with binding allows an efficient stepwise search for the proper structure within the final complex. In higher organisms, many proteins, including some involved in critical aspects of biological regulation and signal transduction, are stably folded only in complex with their specific molecular targets. On page 1021 of this issue, Sugase et al.1 elucidate a three-step mechanism by which one such 'intrinsically disordered' protein binds to its cognate folded protein target.
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