Analysis of opticin binding to collagen fibrils identifies a single binding site in the gap region and a high specificity towards thin heterotypic fibrils containing collagens II, and XI or V/XI

Uwe Hansen; David F. Holmes; Peter Bruckner; Paul N. Bishop

doi:10.1371/journal.pone.0234672

Peer Review History

Original SubmissionMay 29, 2020
10 Jul 2020 Decision Letter - Dragana Nikitovic, Editor PONE-D-20-16285 Analysis of opticin binding to collagen fibrils identifies a single binding site in the gap region and a high specificity towards thin heterotypic fibrils containing collagens II, and XI or V/XI. PLOS ONE Dear Dr. Bishop, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. Please correct minor typographic errors and shortly disccussed why you focused on opticin binding. Please submit your revised manuscript by 20-07-2020. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. 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(Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: Congratulations to the authors for the work on this subject. The authors used electron mircroscopic studies in order to describe opticin binding to fibrillary collagen structures in vitreous and cartilage collagen. Their comments on opticin binding non altering morphology of the fibrillary structures are fascinating and based om measurements of fibril diameter, but is this sufficient to conclude on morphology? Opticin is present in vitreous and cartilage but so is e.g. biglycan, so why did the authors choose to address opticin binding only? Please correct "predominates" to "predominate" on line 64 and "collagen II, IX and IX" to "collagen II, IX and XI" on line 146 ****** 6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. 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Revision 1
20 Jul 2020 Author Response Dear Dr Nikitovic Thank you for your Email concerning our manuscript. You asked us to submit a revised version on the manuscript addressing the points that were raised during the review process. We hope that these have been addressed in the revised manuscript. Below is our response to the specific issues that have ben raised. 1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at These have been checked and I hope they meet with the PLOS ONE style requirement. 2. We note that you have included the phrase “data not shown” in your manuscript. We have removed “data not shown” from line 209 and added in a Supplementary Figure (Fig S5) showing that opticin does not bind to type 1 collagen fibrils. Responses to reviewer’s comments Their comments on opticin binding non altering morphology of the fibrillary structures are fascinating and based om measurements of fibril diameter, but is this sufficient to conclude on morphology? Our previous work has shown that fibril diameter, morphology and molecular composition are interdependent (e.g. Blanschke et al. JBC 2000: 275: 10370-787), so we believe that conclusions can be made on morphology if opticin does not affect fibril diameter. Opticin is present in vitreous and cartilage but so is e.g. biglycan, so why did the authors choose to address opticin binding only? Whilst several members of the small leucine rich repeat proteoglycan (SLRP) family have been identified in vitreous and cartilage, we were particularly interested in studying opticin because in vitreous it appeared to be the major macromolecule associated with the collagen fibrils (Reardon et al 2000). Furthermore, we have shown that in vitreous opticin has anti-angiogenic properties which appear to relate to its collagen binding, so it was deemed important to investigate the binding of opticin to collagen fibrils. An additional reason is that, whilst there is previously published data showing the binding sites of class I and class II SLRPs on collagen fibrils, there is no published data on the binding of class III SLRPs. To emphasise the first of these points (the others have already made in the text), we have added a sentence to the discussion, sentence 2, lines 179 -182, and a reference to a vitreous proteomics study which identified several SLRPs in vitreous. “Whilst several SLRPs are present in vitreous [19], opticin is of particular interest because it was found to be a major component of a pool of macromolecules that strongly associated with vitreous collagen fibrils [1].” Please correct "predominates" to "predominate" on line 64 and "collagen II, IX and IX" to "collagen II, IX and XI" on line 146 Predominates has been changed to predominate We have not made any changes to line 146 as it is not clear what the reviewer would like us to do and as far as we can see it reads satisfactorily. Some other minor corrections have been made to the text including incorrect reference numbers (these are highlighted). Yours sincerely Paul Bishop https://doi.org/10.1371/journal.pone.0234672.r002
24 Jul 2020 Decision Letter - Dragana Nikitovic, Editor Analysis of opticin binding to collagen fibrils identifies a single binding site in the gap region and a high specificity towards thin heterotypic fibrils containing collagens II, and XI or V/XI. PONE-D-20-16285R1 Dear Dr. Bishop, We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements. Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication. An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org. If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. Kind regards, Dragana Nikitovic, Ph.D Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0234672.r003
Formally Accepted
29 Jul 2020 Acceptance Letter - Dragana Nikitovic, Editor PONE-D-20-16285R1 Analysis of opticin binding to collagen fibrils identifies a single binding site in the gap region and a high specificity towards thin heterotypic fibrils containing collagens II, and XI or V/XI. Dear Dr. Bishop: I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org. If we can help with anything else, please email us at plosone@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Dragana Nikitovic Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0234672.r004

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