Circular permutation is a process during evolution that changes the order of amino acids in a protein sequence, resulting in a protein structure with different connectivity, but overall similar three dimensional shape. As a consequence of the circular permutation, the N-terminus of one protein shows significant sequence similarity to the C-terminus of the other and vice versa. Artificially created permutations have been used for various purposes in protein engineering and design. One of the first naturally occurring circular permutations identified was the swaposin family which are circularly permuted versions of saposins.PubMed
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A model that can explain how circular permutations can occur during evolution is gene duplication of a precursor gene.[2] If both genes become fused this leads to a tandem protein. The 5' and 3’ part of the gene can get lost again for example by insertion of a stop codon.
Many protein structures are observed to have their N- and C-termini in close proximity in space.[3] This characteristic contributes that such permutation events can get tolerated. The amino and carboxy termini of the protein are being fused and different termini introduced, while keeping the overall arrangement of secondary structure elements essentially unmodified.
Artificially constructed circularly permuted proteins are being used in protein engineering to stabilize proteins. They have been show to decrease the proteolytic susceptibility of recombinant proteins,[4] They have been used to insert domains into green fluorescent protein.[5] There are several studies that use circular permutations to manipulate protein scaffolds, resulting in improved catalytic activity and altered substrate or ligand binding affinity. Circular permutations have been also used to enable the design of novel biocatalysts and biosensors. For a review on this see.[3]