Basic Residue Clusters in Intrinsically Disordered Regions of Peripheral Membrane Proteins: Modulating 2D Diffusion on Cell Membranes

Round 1

Reviewer 1 Report

I would like to suggest the inclusion of more results from molecular dynamics simulation to the paper.

Author Response

Thank you for the feed back.  In fact a large number of the articles cited are molecular dynamic simulations.  

Reviewer 2 Report

First of all, it is a fascinating and helpful review paper that fully deserves
publishing in Physchem Perspectives issue. However, before publication, there are several issues to address and improve the manuscript accordingly. 

1. I will begin with the List of Publications: unfortunately, very few
references have pages or an equivalent identifier. Most do not.  Please correct!

2. P. 3, line 100: "30% phosphatidylserine". Please compare with Inner leaflet
in Fig. 2. It suggests that PS takes about 10%, maybe, but hardly 30%. Something is wrong.

3. P. 5, line 174 and line 2 in the caption of Fig. 2:  one discusses the
initial 16-peptides of 66 proteins. However, the right part of this figure
describes 15-peptides (I counted only 15 amino acids for each protein). Please, fix the issue.

4. P. 8, line 309: "radius of 10 mM". Please fix the typo: must be micrometer
(not millimolar).

5. P. 8, line 323: "b-sheets": change "b" to Greek beta.

6. P. 8, line 334: In which length is R scaled? Ln(1/R) makes only sense when
you specify this. Under logarithm, there must be a dimensionless quantity.
Hence, 1/R must be a ratio of two lengths. 

7. P. 8, line 350: "Diffusion" should start from the lower case (a typo).

Author Response

Thank you for the feed back and my apologies for the technical problems with the automatic reference program. It was not a problem of the program but of my inexpert using of it. It is now corrected.

Again it was my mistake the 30% PS.  The correct number varies and the number I had in mind was 13% but the value in the figure is actually 10%. Since the actual number is not so important, I have simply eliminated the numbers.

The discrepancy between 16 and 15 residues comes because in the original publication was listed as 16 residues, which is what appears in the gene, but the initial methionine (residue 1) is eliminated before myristoylation of residue 2. I have written the sequence as it would appear in the mature proteins.

The micrometer typo has been corrected

The scaling refers to the relative diffussion coefficients of to proteins differing in their radius. I have slightly rewritten the phrase to alleviate the discomfort of taking the logarithm of a dimensional quantity but I have kept the approximate phrasing of the original reference I was citing.

The typo in Diffusion has been corrected. 

Reviewer 3 Report

The manuscript Basic residue clusters in intrinsically disordered regions of peripheral membrane proteins: modulating 2D diffusion on cell membranes by Miquel Pons reviews the current knowledge about the biological functions of intrinsically disorder regions found in peripheral membrane associated proteins, paying especial attention to the critical role played by basic amino acid clusters found in these disordered regions for such functions.

In my opinion, this is an excellent manuscript, well organized and well written. There are only a few minor suggestions:

 

Line 79: I believe the author can use the acronym PMP for “peripheral membrane proteins”.

 

Line 105: Since this sentence is a general (and important) statement, it will benefit from a bibliographic reference.

 

Line 255: I suggest to eliminate the word “still”. As judged from its context, the next sentence should appear at the same line.

 

Line 309: “…radius of 10 mm…” instead of “…radius of 10 mM…”

 

Line 334: I understand that the letter D used in this line refers to the diffusion coefficient. If that is the case, it should be stated to avoid confusions.

 

Line 385. Probably the following paragraph should be title with “Conclusions”.

 

Author Response

Thank you for the feedback

The acronym PMP has been used

A reference was added for the resting membrane potential. I have actually given a range of values typically found and the reference is to a review paper on the methods that are used to experimentally determine these numbers.

Line 255.  I have accepted the reviewer advice. Thank you for the suggestion.

Line 309. The typo has been corrected

Line 334. The sentence has been slightly modified and the D has been defined.

Line 385.  Again, thanks for the suggestion. It has been incorporated