https://orcid.org/0000-0003-2166-1222
Peer Review History
| Original SubmissionApril 19, 2021 |
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Dear Dr. Schwefel, Thank you very much for submitting your manuscript "Structural insights into Cullin4-RING ubiquitin ligase remodelling by Vpr from simian immunodeficiency viruses" for consideration at PLOS Pathogens. As with all papers reviewed by the journal, your manuscript was reviewed by members of the editorial board and by several independent reviewers. The reviewers appreciated the attention to an important topic. Based on the reviews, we are likely to accept this manuscript for publication, providing that you modify the manuscript according to the review recommendations. Authors are encouraged to consider the suggestion from reviewer #1 to include the sequence alignment (currently in Figure S6) in Figure 6, and should address comments raised by reviewer #2 in the discussion section of the manuscript Please prepare and submit your revised manuscript within 30 days. If you anticipate any delay, please let us know the expected resubmission date by replying to this email. When you are ready to resubmit, please upload the following: [1] A letter containing a detailed list of your responses to all 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. Thank you again for your submission to our journal. 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, Gilda Tachedjian, Ph.D. Associate Editor PLOS Pathogens Richard Koup Section Editor PLOS Pathogens Kasturi Haldar Editor-in-Chief PLOS Pathogens orcid.org/0000-0001-5065-158X Michael Malim Editor-in-Chief PLOS Pathogens *********************** Authors are encouraged to consider the suggestion from reviewer #1 to include the sequence alignment (currently in Figure S6) in Figure 6, and should address comments raised by reviewer #2 in the discussion section of the manuscript Reviewer Comments (if any, and for reference): Reviewer's Responses to Questions Part I - Summary Please use this section to discuss strengths/weaknesses of study, novelty/significance, general execution and scholarship. Reviewer #1: The Vpr/Vpx accessory proteins of HIV/SIV hijack the same CRL4-DCAF1 E3 ubiquitin ligase to mediate degradation of multiple cellular factors to facilitate infection. Previous structural studies with SIVsm Vpx, SIVmnd Vpx, and HIV-1 Vpr by this group and others highlighted that these viral proteins essentially fold and interact with DCAF1 in the same manner, but recruit structurally diverse proteins. Banchenko et al., now detail the molecular architecture of SIVmus Vpr interaction with the CRL4-DCAF1 E3 by conducting integrative structural analyses with X-ray crystallography, cryo-electron microscopy, and cross-linking mass spectrometry. The data show that SIVmus Vpr utilizes the common modality to interact with DCAF1, while it employs unique interface for recruitment of the SAMHD1 C-terminus. The structural data are well supported by biochemical and mutational analyses. The paper is well written with substantial amount of data, which support the major findings. This should be of interest to HIV community as well as ubiquitin field. Reviewer #2: This manuscript reveals the structural insights about the molecular interactions among Cullin4-RING ubiquitination complex (DCAF1), host SAMHD1 protein and an unique SIV Vpr protein harboring SAMHD1 degradation capability, called hybrid Vpr. Both X-ray crystallography and CryoEM methods were employed to gain the understanding of the molecular interaction mechanisms engineered by the hybrid Vpr during SAMHD1 proteosomal degradation. Revealing that this hybrid Vpr establishes different interaction strategies to SAMHD1, compared to well characterized Vpx proteins that degrade host SAMHD1, confirms that strategies adapted by various lentiviruses for counteracting host SAMHD1 proteins were differentially established throughout evolution and escape from the SAMHD1-mediated anti-viral selective pressures. Both methodologies and data interpretations were properly conducted. However, a few issues can be addressed for clarifications and better presentations. ********** Part II – Major Issues: Key Experiments Required for Acceptance Please use this section to detail the key new experiments or modifications of existing experiments that should be absolutely required to validate study conclusions. Generally, there should be no more than 3 such required experiments or major modifications for a "Major Revision" recommendation. If more than 3 experiments are necessary to validate the study conclusions, then you are encouraged to recommend "Reject". Reviewer #1: None Reviewer #2: No major issues. ********** Part III – Minor Issues: Editorial and Data Presentation Modifications Please use this section for editorial suggestions as well as relatively minor modifications of existing data that would enhance clarity. Reviewer #1: Sequence alignment of HIV-1 Vpr, SIVmnd Vpx, SIVsm Vpx, and SIVmus Vpr can be incorporated with Fig. 6, highlighting utilization of different residues at distinct location for specific substrate recruitment, and common or the same residue types for DCAF1 interaction based on the published and current data set. S6 Fig contains such information, however it is too crowded to appreciate the message. Reviewer #2: 1) It is not clear whether dGTP was used during structural analyses. Plus, it is also not clear which form of SAMHD1 is expected in the models presented in Figure 7. If dGTP was not used in any of both biochemical and structural analyses, SAMHD1 dimers could be the form that existed during the analyses. This could be an important issue, particularly because the molecular behaviors of the C-T domain could be significantly different between tetramers (with dGTP) and dimers (without dGTP). 2) It is likely that there is a significant molar ratio difference in infected macrophages between SAMHD1 and Vpr (or Vpx) carried by an infecting virion: SAMHD1 is highly abundant in macrophages whereas Vpr molecule numbers carried by a single virion should be much limited per cell. Therefore, it is not clear whether the model presented in Figure 7 can postulate any scenarios that may explain the degradation dynamics imposed by the vastly different molar ratios between SAMHD1 and Vpr per infected macrophage. Discussion on this issue will be helpful. 3) It remains somewhat unclear whether free Vpr captures SAMHD1 first and then binds to DACF1 in the complex, or Vpr binds to DCAF1 in the complex first and then captures SAMHD1. Possibly the SAMHD1-DCAF1 binding could be more stationary while Vpr binding to SAMHD1 is rather transient. Discussion on this issue will be helpful. 4) The Vpr proteins that carry anti-SAMHD1 activity has been considered as "ancient" Vpr before the gene duplication to create Vpx, leading to its loss of anti-SAMHd1 function. This point needs to be addressed in Introduction for giving a better definition of "hybrid' Vpr. ********** 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 Figure Files: While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email us at figures@plos.org. Data Requirements: Please note that, as a condition of publication, PLOS' data policy requires that you make available all data used to draw the conclusions outlined in your manuscript. Data must be deposited in an appropriate repository, included within the body of the manuscript, or uploaded as supporting information. This includes all numerical values that were used to generate graphs, histograms etc.. For an example see here: http://www.plosbiology.org/article/info%3Adoi%2F10.1371%2Fjournal.pbio.1001908#s5. Reproducibility: To enhance the reproducibility of your results, we recommend that you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. Additionally, PLOS ONE offers an option to publish peer-reviewed clinical study protocols. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols References: Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice. |
| Revision 1 |
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Dear Dr. Schwefel, We are pleased to inform you that your manuscript 'Structural insights into Cullin4-RING ubiquitin ligase remodelling by Vpr from simian immunodeficiency viruses' has been provisionally accepted for publication in PLOS Pathogens. 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 Pathogens. Best regards, Gilda Tachedjian, Ph.D. Associate Editor PLOS Pathogens Richard Koup Section Editor PLOS Pathogens Kasturi Haldar Editor-in-Chief PLOS Pathogens orcid.org/0000-0001-5065-158X Michael Malim Editor-in-Chief PLOS Pathogens *********************************************************** Reviewer Comments (if any, and for reference): |
| Formally Accepted |
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Dear Dr. Schwefel, We are delighted to inform you that your manuscript, "Structural insights into Cullin4-RING ubiquitin ligase remodelling by Vpr from simian immunodeficiency viruses," has been formally accepted for publication in PLOS Pathogens. We have now passed your article onto the PLOS Production Department who will complete the rest of the pre-publication process. All authors will receive a confirmation email upon publication. 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 scientific or type-setting 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. Note: Proofs for Front Matter articles (Pearls, Reviews, Opinions, etc...) are generated on a different schedule and may not be made available as quickly. Soon after your final files are uploaded, the early version of your manuscript, if you opted to have an early version of your article, 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 open-access publishing; we are looking forward to publishing your work in PLOS Pathogens. Best regards, Kasturi Haldar Editor-in-Chief PLOS Pathogens orcid.org/0000-0001-5065-158X Michael Malim Editor-in-Chief PLOS Pathogens |
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