Although some proteins can reach a properly folded state without assistance, many require help to adopt the correct topology and avoid kinetic trapping in nonnative states. Chaperones encapsulate guest proteins and use adenosine triphosphate (ATP)–driven conformational changes to help them fold, but not all chaperones work for all substrates. Balchin et al. compared the folding pathway of the cytoskeleton protein actin with its proper chaperone, TRiC, to the incorrect folding that occurs with the bacterial chaperone GroEL. TRiC functions by stabilizing an extended form of actin with the proper secondary structure and topology. ATP binding and hydrolysis drives release of this partially folded intermediate into the chaperone where it can successfully fold.