cover illustration A PDZ domain was subjected to circular permutation for folding studies. The circularly permuted variant was designed with the specific aim of posing two of the strands participating to the folding nucleus as contiguous elements in the sequence.
A schematic representation highlights the difference in sequence connectivity of PDZ2 and the circularly permuted cpPDZ2.The interaction between beta-strands 1, 4 and 6 (yellow, orange and blue, respectively) was previously identified as a key step in PDZ folding. Data reveal that, although cpPDZ2 is significantly destabilized, a folding intermediate is accumulated and the early folding events are accelerated by two orders of magnitude. For details, please see Ivarsson et al., pp. 155-160.
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