JerMa88/TPR_Peer_Reviews huggingface dataset:
Peer review of: A fungal pathogen induces systemic susceptibility and systemic shifts in wheat metabolome (2019)



REVIEWERS' COMMENTS: 

Reviewer #4 (Remarks to the Author): 

The work presents very novel and very important findings. However, there are some analysis that 
are not clear and conclusions that are still not supported by the results shown. 
The main reason for this comment is that with the analysis presented we cannot differentiate 
between specific induced immunity and induced susceptibility. Chinese Spring is able to specifically 
recognize one avirulence factor of IPO323 and induce an immune response suggesting that the 
observed differences in accumulation of metabolites between the cultivars is due to the immune 
response induced in Chinese Spring and not to the induced susceptibility induced in Obelisk (As 
now indicated in lines 173-174). Having a strong conclusion on the fact that Z. tritici manipulates 
the accumulation of compounds involved in plant defense responses (as indicated in lines 198-
200) is more challenging and I do not think that the provided data demonstrate this. However, I 
agree that the results presented do not contradict this statement and actually go in the good 
direction. The new experiment included in figure S10 is a good example in which Z. tritici might 
suppress the accumulation of a compound (lignin) since there are differences in the accumulation 
pattern in Obelisk between the infected and not infected plants compared to Chinese Spring. I 
think that this kind of comparisons, which incorporate both the treatment and the cultivar, are the 
ones that need to be performed in order to demonstrate the role of metabolites in SIS. And not to 
compare for each treatment or position the accumulation of a certain compound between both 
cultivars. If there are other compounds with a similar accumulation pattern as the one shown in 
Figure S10, it will provide more evidences for SIS and the role of metabolites. 
About figure 6, still is not clear how many times was the experiment performed. If it was only 
performed once, a biological replicate will be needed. I agree that there might have been 
differences at 21 dpi, but extrapolations should not be made with infection assays and the results 
presented do not show differences between both treatments. Thus, the sentence in lines 254-255 
("fungal success on the systemic leaf was increased with infection on the second leaf at 16 dpi") is 
not correct.
Peer review of: The morphology, molecular development and ecological function of pseudonectaries on (2020)



Reviewer #1 (Remarks to the Author): 

I'm perfectly satisfied with the revisions. 

Reviewer #2 (Remarks to the Author): 

Thank you very much for your replies to my comments. I am happy to see that my comments were 
helpful and I am fully satisfied with the changes made to the manuscript. I have no further 
suggestions to make. Congratulations on a very nice study! 
Martin Heil 

Reviewer #3 (Remarks to the Author): 

I am happy with this revised version of this MS. The authors have properly acknowledged the largest 
part of comments and adequately addressed to the very few ones they have not included
Peer review of: miRNA-1-3p is an early embryonic male sex-determining factor in the Oriental fruit fly (2020)

REVIEWERS' COMMENTS:
Reviewer #1 (Remarks to the Author):
Thomas Cline
Reviewer #2 (Remarks to the Author):
The authors have responded remarkably constructively to all the many concerns of the three
 reviewers. Hence the manuscript is much improved in both experimental content, logical presentation,
 and language style and is publishable in its present form. (line 307: functionalLY conserved)
 
In this revised manuscript, Peng et al report the identification of a paternally inherited micro-RNA that
plays a role in sex determination of the fruit fly Bactrocera dorsalis. This is another valuable addition
to the bewildering diversity in gene regulation of sex is determination in insects. My main concerns
have been well addressed:
- The identified micro RNA is clearly involved in sex determination and earlier embryonic time points
will be investigated for the primary signal at a later stage
- miR-1-3p is autosomal based on the genome sequence
- regulation on miR-1-3p in males and females is addressed
- the introduction is now more comprehensively written
- ambiguous terminology has been improved
- methodological issues have been addressed
Reviewer #3 (Remarks to the Author):
The authors have fully addressed my previous comments in this revised manuscript.
Peer review of: A conserved strategy of chalcone isomerase-like protein to rectify promiscuous chalcone (2020)


 
 

 

 

REVIEWERS' COMMENTS: 

Reviewer #1 (Remarks to the Author): 

I am satisfied the revision and I believe that the manuscript is good to publish in Nature 
Communications. 

Reviewer #2 (Remarks to the Author): 

The authors have well responded to the criticism raised. They have carried out additional 
experiments and have properly changed the manuscript.
Peer review of: Interspecific introgression mediates adaptation to whole genome duplication (2019)


REVIEWERS' COMMENTS:  

Reviewer #1 (Remarks to the Author):  

I think the authors have done their utmost best to address all my concerns (as well as those of the 
other reviewers, which I looked at as well), and I have no further comments.  

Reviewer #2 (Remarks to the Author):  

The revision addressed all my concerns, I am satified with the updated manuscript.
Peer review of: Reverse engineering synthetic antiviral amyloids (2023)



REVIEWERS' COMMENTS: 

Reviewer #3 (Remarks to the Author): 

Authors have addressed most of my concerns and performed additional experiments. 

Reviewer #4: 

This reviewer submitted a confidential document, which highlights some remaining points based on 
your response to the points raised by reviewer #2: 
Point 3: While you now explain that Aspartic acids were added, please explain why adding these 
negative charges is beneficial. Also, when you first describe peptide 12, please explain in which 
functional domain of the IAV PB2 this sequence is lying. Also,specify what is the corresponding 
sequence in influenza B. 
Point 5: The reviewer agrees with reviewer 2 that two-fold reduction in PFU (lung virus titer) is 
minimal, and it is very hard to believe that this effect was significant. If you want to keep the in 
vivo results, you should use much more subtle wording and explain that the in vivo effect was 
‘marginal’. [Editorially we think that it is okay that the synthetic amyloid is not quite ready for 
therapeutic demonstration in vivo, and ask that you caveat and walk back this claim. 
All other points were judged to be addressed, or editorially overruled. There was a request to use 
VX787 as a positive control in Fig 3f, but as additional experiments at this time are not feasible 
and the absence of this control will not alter the overall message, we decided that it was not 
necessary.
Peer review of: Tetrameric architecture of an active phenol-bound form of the AAA+ transcriptional (2020)



Reviewers' comments: 

Reviewer #2 (Remarks to the Author): 

The authors have addressed many technical issues in the new version of manuscript. This makes 
things better. However there are still several significant concerns to be clarified. 

1. ATP or its analogues are not included in the structure. Since ATP is critical for the transcription 
the lack of ATP make it difficult to draw the conclusion that the tetramer is an active form. Did the 
authors try negtive-stain electron microscopy to see if ATP trigger any conformational change or 
formation of hexamer? 

2. Why does DmpR form tetramer while other AAA+ ATPase transcriptional regulators are 
hexamer? There should be some structural basis for the difference. 

3. The auther did not discuss the significant inconsistence between this work and the result 
reported by ref 13. In ref 13 Wikstrom et al mentioned that both tetramer and hexamer had been 
observed and only the hexamer is active. 

4. The PDB access number for this structure should be 6IY8 rather than 6IYB.
Peer review of: An evolutionary path to altered cofactor specificity in a metalloenzyme (2020)


 

REVIEWERS' COMMENTS: 

 

Reviewer #3 (Remarks to the Author): 

 

Anna Barwinska-Sendra and co-workers present a corrected version of their previous manuscript 
entitled “An evolutionary path to altered cofactor specificity in a metalloenzyme”. They have, in the 
current version, addressed all the reviewer’s requests and I have no further remark or question. This 
manuscript is a very neat study and should deserve publication. 

 

 

Reviewer #4 (Remarks to the Author): 

 

Specific Comments to Address 

Point 16. The authors have tried to measure the redox potential and thoroughly demonstrated the 
difficulty in obtaining such measurements. Text was included now in the main article to explain to 
the reader why this important parameter is missing. A new supplementary Figure 8 was added to 
help address the problem. I am satisfied with their response to this question. 

Point 17. This is similar to point 16, see my comment above. 

Point 18: Given that the redox potentials cannot be measured, Figure 5 provides at least proof that 
the electronic environment is significantly altered. At this stage, without the redox potentials, this is 
all that can be said so Figure S5 provides indirect evidence and thus is worthy of inclusion. I 
therefore accept the author’s response. This is now also supplemented by a new Figure 8 
(Supplementary) which also trends in the correct direction. 

Point 19: This was fixed, satisfied 

Point 20: This was addressed and data are provided in Supplementary Table 5. 

Point 21: fixed 

Point 22: I accept the response given and their conclusions, it is also backed up by references so I am 
happy with the second order perturbation equation approach for the purpose they are using it for. 

 

 

The points raised in my review (some of which were raised by the other reviewers) have been 
addressed and where data is difficult to obtain it is now adequately discussed, so the reader can 
better appreciate the work. The main point of the paper, showing different metal specificity of the 

two enzymes and how this is influenced by reciprocal amino acid substations is robust work and will 
be of interest in my opinion to the readers of Nature Communications. I therefore now recommend 
this article for publication.
Peer review of: Relaxed sequence constraints favor mutational freedom in idiosyncratic metazoan (2020)



REVIEWERS' COMMENTS: 

Reviewer #1 (Remarks to the Author): 

The authors have now addressed all my concerns and toned down the claims substantially, as 
suggested! 

Reviewer #3 (Remarks to the Author): 

The authors have thoroughly addressed all of my concerns and I recommend publication.
Peer review of: Photoinduced monooxygenation involving NAD(P)H-FAD sequential single-electron transfer (2020)

Reviewers' comments: 

Reviewer #1 (Remarks to the Author): 

The authors have suitably answered my comments. Therefore, I have no objections to publish this 
manuscript. 

Reviewer #2 (Remarks to the Author): 

This paper is a reviewed version of a manuscript that describes unanticipated light dependent 
NADPH reduction of flavin. Nicotinamide mediated flavin reduction is a very common reaction 
normally understood as a hydride transfer step, while the fact light can influence or even drive 
enzyme activity is something that is becoming a hot topic (be it artificial or natural). 

As such, this manuscript provides interesting angle: an apparently standard flavoenzyme requires 
blue light to be reduced by NADPH. The authors spend considerable effort in characterising this in 
detail and propose a single electron transfer mechanism. 

To what extend this applies in vivo remains to be established, as well as the finer details of the 
mechanism here. However, the revised version addressed the detailed comments previously made 
by the three reviewers in a very constructive manner and the main conclusions are solidly 
supported by the data. 

I recommend publication. 

Reviewer #3 (Remarks to the Author): 

Overall, the authors have adequately addressed most of the issues that I mentioned in my review. 
However, I would like to have clarification on the following points before recommending 
publication. 

Page 6, Line 156: I am still having difficulty understanding the relative rates of the enzymatic and 
the non-enzymatic reactions. I would expect that the relative rates would be largest when the 
enzyme is saturated. This does not seem to be the case. The authors make their measurement at 
[NADPH]=7.8 µM but the Km for NADPH is 158 µM. Please explain. 

Figure 2, Legend, Line 131: I assume that the experiment in panel D (dotted lines) is for the non-
enzymatic reaction and uses [FAD] = [PqsL]. If so, that is an important control experiment. 
However, it demonstrated that the enzyme has only a very small effect on the reaction rate. This 
needs clarification. 

Page 14, line 382: A solvent deuterium isotope effect of 50 is unprecedented (as far as I know) in 
enzyme-catalyzed reactions and merits discussion. How does this number compare with the 
isotope effect on the non-enzymatic reaction?
Peer review of: Siroheme synthase orients substrates for dehydrogenase and chelatase activities in a (2020)

Reviewers' comments:
Reviewer #1 (Remarks to the Author):
Reviewer #3 (Remarks to the Author):
 The authors appear to have addressed all the issues that were raised and have produced a
 significantly improved manuscript.
The revised manuscript by Pennington et al. has addressed some, but not all of this reviewer’s
concerns. There is still concern about the density for the precorrin-2 and Co-sirohydrochlorin, as the
contour level of the Polder maps is lower than usually displayed. Also, in reading the comparison of
the B-factors to that of protein (Fig 2 legend) one would assume that the occupancies were set as 1.0,
(see comment below) then the B-factors for the density are reasonable. However, looking at the PDB
file for Co-sirohydrochlorin it seems that the occupancy was set to 0.5- so the B-factors would be even
higher with an occupancy of 1.0. The authors are cautious about overinterpretation in their wording,
but still I feel that they should be forthcoming about occupancy and B-factors resulting from the poor
density. It is difficult to judge even with validation reports, how good the data for the ligands
themselves is- as the majority of the total diffraction comes from the protein. The authors should also
check throughout to remove colloquial phrasing as discussed below. Comments the authors should
consider follow (page numbers from pdf merged for review):
Page: 4- The authors replaced description of dimer in results as domain swapped- but in the
introduction here the molecule is still described as "an X-shaped molecule, where positioning of the
Rossmann fold from one subunit over the helical domain from the opposing subunit creates a large
cavity. I think it should also be described here as a domain-swapped dimer.
Page: 18- “the activity site less rigid by unfolding helix 6" should probably read "...active site..."
Please check throughout typos
Page 19- Please remove imprecise language- "The bulkier histidine projects into the active site,
landing about where the pyrrole nitrogens are when the molecule binds, so would also disrupt
tetrapyrrole binding and release" should remove the word landing and replace with positioned and end
of sentence should be corrected. Should read something like- "The bulkier histidine projects into the
active site, and is positioned in place of the pyrrole nitrogens when tetrapyrole binds, thus likely
disrupting tetrapyrrole binding and release."
Page: 38- The polder maps in Figure 2 d-f are all contoured at 2 sigma- but it is more usual to contour
at 3 sigma- Is the quality of the density good at three sigma as well? If so, please display contoured
at 3 sigma. Also please note in the Figure legend of Figure 2 when B-factors are described that the
occupancy of the ligands was set to 0.5. It may be more appropriate to set the occupancy to 1.0 and
report the higher B-factors. The authors should be forthcoming about the quality of the ligand density.
Page: 39- Figure 3B- proline 133 is drawn as protonated- please remove the proton
Peer review of: Legionella effector MavC targets the Ube2N~Ub conjugate for noncanonical ubiquitination (2020)


Reviewers' Comments: 

Reviewer #1: 
Remarks to the Author: 
The authors have addressed my concerns. Although they hope to use the crystallographic statistics 
they reported in the old manuscript, I think it is OK, given that the final structural model is the 
same. The manuscript is now suitable for publication.
Peer review of: A deubiquitylase with an unusually high-affinity ubiquitin-binding domain from the scrub (2020)



 

REVIEWERS' COMMENTS: 

 

Reviewer #1 (Remarks to the Author): 

 

NCOMMS-19-37565A 

Review comment: 

Berk et al., “A Deubiquitylase with an Unusually High-affinity Ubiquitin-binding Domain from the 
Scrub Typhus Pathogen Orientia tsutsugamushi” 

 

All my concerns have been properly addressed in the revised manuscript. However, I raise some 
points for improvement of terminologies as follows: 

 

1. Alphabets indicating coefficients, constants and space groups are traditionally italicized (e.g. ‘K’d, 
‘CC’1/2, ‘P’21212, mean ‘I’, and so on). 

 

2. In Table 1, a Greek alphabet should be used for “sigma”. Percentage representation is not suitable 
for CC1/2. The unit of B factors (i.e., Å2) should be presented. 

 

3. In the Methods section, the name of the column for gel-filtration chromatography ‘S75’ is not 
accurate, and should be corrected to ‘Superdex 75’. 

 

4. The isolated OtDUB domains are termed ‘polypeptides’ in some sections and ‘OtDUB fragments” 
in other sections. Please use either one. I favor the latter. 

 

5. In the legend for Supplementary Figure 6, ‘... for enzymatic analyzes were ...’ should be corrected 
to ‘... for enzymatic analyses were ...’. 

 

 

 

Reviewer #2 (Remarks to the Author): 

 

Berk and Lim et al. have made significant improvements to their detailed analysis of the OtDUB Ub 
binding sites and their roles in regulating and specifying DUB activity. My comments have been 
nicely addressed and I only have two minor points for the authors’ consideration. 

 

1) To explain the enhanced cleavage of longer K48 chains, instead of a VR-2:UbS2 interaction that 
would be rotated compared to their structure, could there instead be an S2’ site that dictates K48 
specificity between the S1’ and S2’ positions? If so, one would predict that DUB activity toward long 
K48 chains would be “exo” in nature whereas K63 cleavage would be “endo”, and this might explain 
the observation in Fig 3C that K63 cleavage stalls at diUb while K48 cleavage releases monoUb. 

2) It’s possible that I missed it, but I could not find a reference to Fig 2C in the text. 

 

 

 

Reviewer #3 (Remarks to the Author): 

 

The authors have addressed all my concerns and provided additional data to support their findings. 
The manuscript is suitable for publication. 

 

Minor comments 

1. Figure 6f comes before Figure 6e in the text. 

2. Typo "Abode Photoshop" in the methods
Peer review of: Btk SH2-kinase interface is critical for allosteric kinase activation and its targeting inhibits B- (2019)



REVIEWERS' COMMENTS: 

Reviewer #1 (Remarks to the Author): 

All of my queries/concerns have been adequately dealt with 

Reviewer #2 (Remarks to the Author): 

The authors have satisfactorily answered most of my queries. I still have some concerns regarding the 
effect on phosphorylation on Y551 versus Y223 in BTK and the phosphorylation of the substrate 
PLCG2. However, given that the manuscript describes a novel mechanism of regulation for BTK, it 
seems unreasonable to demand full explanation for every measurement and observation. The 
manuscript contains many interesting features, apart from what was already mentioned, also new 
data on the structure of BTK. 

C. I. Edvard SMITH 

Reviewer #3 (Remarks to the Author): 

The authors have provided additional mutagenesis data supporting the SH2 domain-kinase N-lobe 
interaction that stimulates catalytic activity, although it is not surprising that a mutation such as 
I429E, which lies in the 'hydrophobic core' of the N lobe, disrupts kinase activity, probably because it 
disrupts intrinsic catalytic activity, not because the allosteric interaction with the SH2 domain is lost 
(or at least not exclusively). 

The authors suggest that L405E in the kinase N lobe might hyperactivate the kinase domain by 
hyperstabilizing the interaction with the SH2 domain. They mention in the text the possible interaction 
between L405E and positively charged residues in the SH2 domain, citing Suppl. Fig. 3n, yet this 
figure does not show the location of the positively charged residues. The authors might want to modify 
this figure to do so.
Peer review of: ABCG2 transports anticancer drugs via a closed-to-open switch (2020)


 
 
 
 
  
 
 

REVIEWERS' COMMENTS: 
 
Reviewer #1 (Remarks to the Author): 
 
The authors have painstakingly addressed every point I raised and with the additional clarity this 
brings to the manuscript I believe this now better presents their outstanding research. 
 
 
Reviewer #2 (Remarks to the Author): 
 
The authors have satisfactorily addressed all my concerns. The manuscript has been improved 
substantially. I, therefore, strongly support the publication of this manuscript.