Talk:Circular permutation in proteins

Redlinks
Several of the links to people on wikipedia are currently pointing to unrelated people who happen to have the same name. What do we link to if the page is not in WP yet? Shall we just remove the links again? --Andreas 07:40, 18 November 2011 (PST)
 * I recommend we just remove links to topics not in wikipedia, at least for now. Although a few red links in the published paper might provide suggestions for future Topic Pages to other authors. Spencer Bliven 17:20, 18 November 2011 (PST)

Changes for Wikipedia
Before being transfered to wikipedia, the following changes will be made:


 * Remove authors
 * Remove Acknowledgements
 * Remove "wp:" prefix from links
 * Add attribution - either by way of the generic template OA-attribution or by a PCB-specific one
 * Provide metadata for figure upload
 * Reformat references. If they have a DOI, Cite doi may be the simplest solution. Otherwise, cite book, cite web etc. may be necessary.
 * Switched references to Template:cite pmid, which also exists on wikipedia. --Spencer Bliven 17:42, 24 January 2012 (PST)

Reviews
Spencer, below you'll find Rob Russell's review. I am awaiting to hear from one other reviewer, shortly. Please await to hear from the other reviewer before implementing any changes to this page.

Review by Rob Russell
This page describes circularly permuted proteins and for the most part is a good starting point for this subject. However, I have several comments.

The first line reads "Circular permutation is a process during evolution  that changes..." I think strictly speaking it isn't an evolutionary process, but a description of the relationship between proteins that sometimes is a clear evolutionary process (sometimes a post-translational one, which I get-it is also evolutionary in some sense; at other times they are engineered as the author points out). The first permutation (concanavalin A) is more of a functional modification. I think a better opener would be to speak of it as a relationship between proteins. in other words, "Circular permutation in proteins describes the situation where one protein is circularly permuted relative to another related protein." (and then ellaborate on the other points)

I would perhaps mention that the post-translational modification of concanavalin A is a cleavage and an unusual protein-ligation (there are, I presume, suitable cross-references here too).

Re: the Swaposin story, Russell has two Ls, and I would avoid the non-wikipedia subjectivity statements like "lighthearted" - I would just say nicknamed. These are the kinds of things that get flagged in Wikipedia - the stuff has to read like an encyclopedia and not an editorial.

Re: Programmatic detection. I think this English is a bit dubious and perhaps the section would be more appropriately headed "Detection of Circular Permuations" (or similar). This section could also do with some slightly longer introduction about why it is problematic to detect these using standard techniques like dynamic programming, etc. And one reference in this list is missing which I believe to be the first method to detect permutations: Michael Zuker, JMB 221:403-420, 1991 Suboptimal sequence alignment in molecular biology: Alignment with error analysis.

The figure showing Concanavalin A and Lectin is a little hard to understand - it might be easier to use a two color (N- and C- terminus) rather than a color ramp, but perhaps this won't help - worth trying perhaps.

Review by BK Lee
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. -

Spencer, the review process is complete. Please modify your pages, provide me with details about the modifications that you introduced either by e-mail, or on the discussion page of the revised version (Don't know exactly who this works..), and send me the link to the revised version.

Response to reviewers
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.

A full diff of the revisions made can be viewed at

Dr. Russell

 * 1) First line. The lead section has been reworded to make clear that circular permutation is a relationship between proteins. This was an excellent point, and we have striven to make clear what is being permuted more consistently throughout the article. The lead section was also changed to mention other processes which can lead to circularly permuted proteins.
 * 2) Concanavalin A mechanism. The auto-catalysis of Concanavalin A is mentioned in the PTM section, and the history section now also mentions it.
 * 3) Swaposin. Apologies for the typo in your name in this section. We have removed the word "lighthearted".
 * 4) Programmatic Detection of Circular Permutations. The section name has been expanded, and the text rewritten and expanded. Thank you for the reference to FBPLOT, which we were previously unaware of.
 * 5) Conanavalin A figure. We have rerendered this figure using a more gradual color gradient and with spheres marking the termini. This seems a little clearer to us.

Dr. Lee

 * 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

Other modifications
In addition to addressing the comments from the reviewers, the following sections were added or heavily modified. We would welcome any additional comments on these sections.


 * 1) Examples for both evolutionary mechanisms are described in detail: Saposin and Swaposin for Permutation by Duplication, and Transhydrogenases for Fission and Fusion
 * 2) Bullet points in the protein engineering section were explained in more detail, in an attempt to reduce the use of jargon.

--Spencer Bliven 18:29, 14 December 2011 (PST)

--Andreas Prlić 18:38, 14 December 2011 (PST)

Further comments
--Daniel Mietchen 05:00, 3 January 2012 (PST)
 * The file name File:ConcanavalinALectin.png is already taken on Commons, and spaces or dashes are preferred in Commons file names anyway, so as to make them more descriptive.
 * An old version of ConcanavalinALectin.png exists on wikipedia and will be replaced by the version here. It is not taken on commons (perhaps you were looking at commons:File:Concanavalin A.png or commons:File:3CNA Concanavalin A.png) --Spencer Bliven 11:33, 3 January 2012 (PST)
 * The PubMed extension does not always seem to fetch proper metadata (not sure whether the problem is on its side or at NCBI, though), so typesetting will have to keep in mind that reference metadata needs checking. For instance, reference 3965973 (Carrington et al., 1985) is being displayed without the year.
 * Should File:Permutation by Duplication.svg and File:Fission & Fusion.svg get some representation of start and stop codons?
 * I think this would clutter the image. Rather, we could deemphasize start and stop codons in the caption (eg "Next, redundant sections of the protein near the termini are lost, resulting in a circularly permuted gene.") --Spencer Bliven 11:33, 3 January 2012 (PST)
 * In order to be eligible for being featured under Did you know, the current Wikipedia article has to be expanded at least 5-fold within 10 days. The exact threshold is being determined by an automated tool and we are near that factor of 5, so some brushing to meet the criterion might be necessary after posting.
 * What about renaming the "Programmatic Detection of Circular Permutations" section into "Algorithmic Detection of Circular Permutations"?
 * I'm for it. --Spencer Bliven 11:33, 3 January 2012 (PST)

Did you know...
I count 1740 prose words in the current version and 275 in the wikipedia version. We expanded the page by a factor of 6.3. I think we fullfil the other requirements for a DYK as well, so we should prepare a good hook.

Possible hooks:
 * ... that the protein Concanavalin A cuts itself in half and then reassembles in a circularly permuted order?
 * ... that swaposin is a circularly permuted variant of a saposin?
 * ... that David Goldenberg and Thomas Creighton created the first artificial circularly permuted variant of a protein in 1983?
 * ... that the CE-CP algorithm can be used to align pairs of circularly permuted proteins?

Reviews, 2nd round
The revised version is great. Very clear and informative.

I would only recommend a small change in the definition of circular permutations, as follows:

“amino acids in their protein sequence, such that the sequence of the first portion of one protein (adjacent to the N-terminus) is related to that of the second portion of the other protein (near its C-terminus), and vice versa.”

Published!
This article was published at http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1002445 and Circular permutation in proteins.