Virtual Screening of Protein Data Bank via Docking Simulation Identified the Role of Integrins in Growth Factor Signaling, the Allosteric Activation of Integrins, and P-Selectin as a New Integrin Ligand

Round 1

Reviewer 1 Report

This is a well-written review discussing how the binding of specific growth factors and inflammatory factors to a subset of integrins regulate signaling by their cognate receptors.

 

Comments

1.      The authors should delete the section  " How to Use this Template" that follows their Abstract. Also the authors did not follow the formatting instructions.

 

2. Figure 1 – The labeling and legend should be improved, especially for the middle complex.  For instance, what does alpha2beta2 tetramer disulfide-linked refer to?

Author Response

 

 

 

Author Response File: Author Response.pdf

Reviewer 2 Report

The review reports an overview on the available studies concerning the interaction of integrins with growth factors, inflammatory factors or selectins to build ternary complexes involved in cellular events. This research field has been mainly explored by the authors and for this reason the number of self-citations is quite high, anyway the identification of an allosteric activation mechanism in integrins is a topic of great interest and for this reason this review deserves to be published and it will probably pioneeer further studies in the field of protein-protein interaction regulation.  The manuscript is not very easy for the reader and some changes are suggested as below:

1. A clearer introduction explaining the used approach (PDB screening to identify integrin binding factors) and the "take home" massage that the authors would like to give should be added at the beginning of the text

2. In the first section, page 2, line 60-61, the sentence is not clear and should be rewritten to help the reader. Moreover, in the text a very general discussion doesn't correspond to the specific concepts reported in Figure 1 and its label. Some explanation on the three complexes reported in the picture should be added also in the main text.

3. Page 3, as before, a discussion on figure 2 should be added in the main text and details should not only be reported in the figure label.

4. Page 4, the discussion about CD40L (from page 4 to page 6) could be shifted after the paragraph that discusses the experiments on CX3CL1-avb3 integrin interaction (now at page 6-7). In this way, the discussion about CX3CL1 is not interrupted. 

5. Figure 3 should be shifted to page 6, line 186, where HIGM1 mutants are taken into consideration.

6. Page 9, line362, the explanation for figure 5 should be changed, since also the figure label is very generic

7. The concept of allosteric activation, explained in the label for figure 6, should be claimed and emphasized also in the conclusions, since it's the real focus of the review.

Minor typing mistakes:

- Page1, section 0 with editorial instructions has to be removed

- Page 2, line 65, figure 1 caption, the symbol font for integrin a6b4 is missing

-Page 5, line 150, integrin binding is superscript

-Page 6, the section about ELISA is the only one in all the paper with an underlined title, I suggest to remove the title and start the discussion from the following sentence (...To study...)

After revising the text according to this suggestion, the manuscript should be in my opinion fully suitable for publication.

 

 

English language is fine

Author Response

 

 

 

Author Response File: Author Response.pdf