Circular permutation of a WW domain: folding still occurs after excising the turn of the folding-nucleating hairpin.

A hyperstable Pin1 WW domain has been circularly permuted via excision of the fold-nucleating turn; it still folds to form the native three-strand sheet and hydrophobic core features. Multiprobe folding dynamics studies of the normal and circularly permuted sequences, as well as their constituent hairpin fragments and comparable-length β-strand-loop-β-strand models, indicate 2-state folding for all topologies. N-terminal hairpin formation is the fold nucleating event for the wild-type sequence; the slower folding circular permutant has a more distributed folding transition state.