Peer Review History
Original SubmissionNovember 26, 2020 |
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Dear Prof. Helms, Thank you very much for submitting your manuscript "How does Sec63 affect the conformation of Sec61 in yeast?" for consideration at PLOS Computational Biology. As with all papers reviewed by the journal, your manuscript was reviewed by members of the editorial board and by several independent reviewers. In light of the reviews (below this email), we would like to invite the resubmission of a significantly-revised version that takes into account the reviewers' comments. We cannot make any decision about publication until we have seen the revised manuscript and your response to the reviewers' comments. Your revised manuscript is also likely to be sent to reviewers for further evaluation. When you are ready to resubmit, please upload the following: [1] A letter containing a detailed list of your responses to the review comments and a description of the changes you have made in the manuscript. Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out. [2] Two versions of the revised manuscript: one with either highlights or tracked changes denoting where the text has been changed; the other a clean version (uploaded as the manuscript file). Important additional instructions are given below your reviewer comments. Please prepare and submit your revised manuscript within 60 days. If you anticipate any delay, please let us know the expected resubmission date by replying to this email. Please note that revised manuscripts received after the 60-day due date may require evaluation and peer review similar to newly submitted manuscripts. Thank you again for your submission. We hope that our editorial process has been constructive so far, and we welcome your feedback at any time. Please don't hesitate to contact us if you have any questions or comments. Sincerely, Alexander MacKerell Associate Editor PLOS Computational Biology Nir Ben-Tal Deputy Editor PLOS Computational Biology *********************** Reviewer's Responses to Questions Comments to the Authors: Please note here if the review is uploaded as an attachment. Reviewer #1: This work investigates the effects of bounded Sec63 on the conformational dynamics of Sec61 channel through MD simulations. The translocation mechanism of Sec61/SecY complex is very complicated that involves the cooperation between partners in complex, and remains unclear so far. In this paper, the authors analysed the position and orientation changes of involved TM helices by the data comparison. The results will provide insights on understanding the translocation mechanism. The data of the simulations is reliable. However, the discussion about the mechanism how the interaction between Sec63 and TM4 effect the conformational change of pore ring, lateral gate is not convincing. Few issues need to be addressed before the manuscript can be accepted. Major issues: 1. For the free simulations (Sec61 complex without Sec63), the authors simply removed Sec63 from the bound structure (PDB ID: 6N3Q). This will result in position and orientation changes of pore ring, lateral gate and plug. In the Fig. 1, the equilibrated structure is reached at around 600 ns of 1 μs simulations. But the data only the last 50 ns was used to be analysed. 2. In the Fig. 3, authors said "the contacts at IS2, IS3 and IS4 were well maintained, likely due to the regular secondary structure..." (see line 272-279), and the contact at IS1 was not stable that is related to the missing of some residues. The authors should show the region of bilayer in Fig. 3(a). The bilayer could make the contact more stable if the interaction site is located in the bilayer. The fluctuation of Fig. 3(b) likely due to the solvent too. 3. In the Fig. S4, the RMSF in the region near the IS1 and IS3 should be magnified to show the significant difference between the bounded and free state. 4. In the part of "Resilience of the pore-ring and lateral gate", the interaction between Sec63 and TM4 of Sec61 makes the θTM2 change. Then, it makes the dnTM2-nTM10 and dnTM2-nTM4 longer, but the dnTM5-nTM7 shorter. It seems disagree with the cryo-EM structure (line 350). The discussion of this part is not convincing. Does the Sec63 make the dnTM2-nTM7 longer? How the Sec63 makes pore and lateral gate wider is still not clear. Figures of the dnTM2-nTM7 and the diameter of the pore (like Fig. 6,7) should be helpful to current discussion. Minor issues: Two minor spelling mistakes: line 113: "Ssh1" should be "Sss1". line 655: "θTM7" should be "θplug". Reviewer #2: In this paper, the authors have combined molecular modeling, i.e., docking and MD simulations, with co-precipitation experiments on the Sec complex especially focusing on Sec61 and Sec63 in yeast. The conformations and their changes of Sec61 and the effect of the binding of Sec63 to Sec61 were at the heart of this study. The simulations do show interesting changes in the plug conformations depending on the presence/absence of Sec63 especially also of the lateral gate. Thus, the present study adds some nice pieces to the understanding of the translocon and its accessory proteins. - Add a brief summary of the experimental findings to the Author Summary and the Conclusion section. A more detailed combination of theory and experiment in the main text would be helpful for the reader. - I would strongly suggest to include Fig S1 but also Fig S3 to be included in the main text. The reader needs to get a chance to get acquainted with the proteins and one cannot expect the reader to look into the SI for such basic figures. Concerning Fig S1 I would suggest to make the membrane a bit more visible. - Could the channel in Sec61 be characterized by a radius profile? Is anything known about its ion conductance? Other than this, the manuscript is timely and interesting and certainly deserves publication. ********** Have all data underlying the figures and results presented in the manuscript been provided? Large-scale datasets should be made available via a public repository as described in the PLOS Computational Biology data availability policy, and numerical data that underlies graphs or summary statistics should be provided in spreadsheet form as supporting information. Reviewer #1: None Reviewer #2: Yes ********** PLOS authors have the option to publish the peer review history of their article (what does this mean?). 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Revision 1 |
Dear Prof. Helms, We are pleased to inform you that your manuscript 'How does Sec63 affect the conformation of Sec61 in yeast?' has been provisionally accepted for publication in PLOS Computational Biology. Before your manuscript can be formally accepted you will need to complete some formatting changes, which you will receive in a follow up email. A member of our team will be in touch with a set of requests. Please note that your manuscript will not be scheduled for publication until you have made the required changes, so a swift response is appreciated. IMPORTANT: The editorial review process is now complete. PLOS will only permit corrections to spelling, formatting or significant scientific errors from this point onwards. Requests for major changes, or any which affect the scientific understanding of your work, will cause delays to the publication date of your manuscript. Should you, your institution's press office or the journal office choose to press release your paper, you will automatically be opted out of early publication. We ask that you notify us now if you or your institution is planning to press release the article. All press must be co-ordinated with PLOS. Thank you again for supporting Open Access publishing; we are looking forward to publishing your work in PLOS Computational Biology. Best regards, Alexander MacKerell Associate Editor PLOS Computational Biology Nir Ben-Tal Deputy Editor PLOS Computational Biology *********************************************************** Reviewer's Responses to Questions Comments to the Authors: Please note here if the review is uploaded as an attachment. Reviewer #1: In the revised manuscript, the authors carried out a comparison and analysis of distances and angles from last 50 ns and 400 ns respectively, and added distribution plots of dnTM2-nTM7 and pore-ring and a radius profile of channel. The complementary data and analysis makes conclusion more reliable and clear. The explanation for the mechanism of conformational changes is also reasonable. I would like to suggest publication. Reviewer #2: The manuscript has been improved considerably and I now recommend publication as is. ********** Have all data underlying the figures and results presented in the manuscript been provided? Large-scale datasets should be made available via a public repository as described in the PLOS Computational Biology data availability policy, and numerical data that underlies graphs or summary statistics should be provided in spreadsheet form as supporting information. Reviewer #1: Yes Reviewer #2: None ********** 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. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: No Reviewer #2: No |
Formally Accepted |
PCOMPBIOL-D-20-02132R1 How does Sec63 affect the conformation of Sec61 in yeast? Dear Dr Helms, I am pleased to inform you that your manuscript has been formally accepted for publication in PLOS Computational Biology. Your manuscript is now with our production department and you will be notified of the publication date in due course. The corresponding author will soon be receiving a typeset proof for review, to ensure errors have not been introduced during production. Please review the PDF proof of your manuscript carefully, as this is the last chance to correct any errors. Please note that major changes, or those which affect the scientific understanding of the work, will likely cause delays to the publication date of your manuscript. Soon after your final files are uploaded, unless you have opted out, the early version of your manuscript will be published online. The date of the early version will be your article's publication date. The final article will be published to the same URL, and all versions of the paper will be accessible to readers. Thank you again for supporting PLOS Computational Biology and open-access publishing. We are looking forward to publishing your work! With kind regards, Katalin Szabo PLOS Computational Biology | Carlyle House, Carlyle Road, Cambridge CB4 3DN | United Kingdom ploscompbiol@plos.org | Phone +44 (0) 1223-442824 | ploscompbiol.org | @PLOSCompBiol |
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