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closeReviewer 2: Dr. BK Lee
Posted by PLOS_CompBiol on 30 Mar 2012 at 09:36 GMT
[This is a review of the original version - see Text S1 for the version history]
Circular permutation is a process during evolution ... Concur with Robb Russell. Circular permutation is not just an evolutionary process, since it can be made in the laboratory by engineering, as the article shows later.
Circular permutation ... changes the order of amino acids ... A process that changes the order of the amino acid residues would be called simply as a permutation. Circular permutation is a particular kind of permutation, wherein the N- and C- termini of one protein is found joined together in another that is homologous.
Genetic mechanism of circular permutation One could add exon shuffling as another potential mechanism.
Among the motivations for engineering circular permutation One could mention not only the order in which it folds, but also its effect on folding kinetics (with reference to some of Howard K. Schachman's work).
"Programmatic" detection of circular permutation Concur with Robb Russell.
RE: Reviewer 2: Dr. BK Lee [Author Response]
PLOS_CompBiol replied to PLOS_CompBiol on 30 Mar 2012 at 09:40 GMT
[These are the author responses, which are reflected in the published version]
Thanks to Dr. Russell and Dr. Lee for their helpful reviews of our topic page. The manuscript has been significantly rewritten in response to their comments.
1. Lead section problems. The lead has been rewritten to better define circular permutation as a relationship between proteins.
2. Exon shuffling. Exon shuffling is now mentioned in the evolution section as a proposed mechanism. Shuffling does seem a plausible explanation for the evolution of circular permuted proteins (although the distinction between the permutation by duplication and exon shuffling seems fuzzy at best), however we were unable to find any experimentally validated examples of exon shuffling leading to a circularly permuted protein.
3. Effect on folding kinetics. References to Schachman's work have been included in the artificial CPs section .