From Antibodies to Crystals: Understanding the Structure of the Glucocorticoid Receptor and Related Proteins

Round 1

Reviewer 1 Report

The understanding of the structure of nuclear receptors is very important for human health. The manuscript focuses on the contributions made by Jan-Å ke Gustafsson and colleagues to the field of structural study mainly on glucocorticoid receptor and a section on LXR-RXR complex. The author summarized all of these well. Nevertheless, the title of the manuscript seems too big since only GR and LXR-RXR complex have been involved. Or the structure generation story of other nuclear receptors such as ER, AR, and so on, should be also summarized.

Author Response

The reviewer makes a very good point about the original title, and this has been changed to better reflect the content of the manuscript.

The idea of a more comprehensive review on the ‘structure generation story’ of steroid receptors would be both interesting and a valuable addition to the literature, but I feel that is beyond the focus of the present manuscript.

Reviewer 2 Report

Glucocorticoid receptor is an evolutionarily conserved nuclear receptor involved in regulation of gene transcription. The author reviewed the important progress of the structural mechanism of glucocorticoid receptor. This review is well written. However, I still have a few concerns.

1. Could the author label in the figures the helices/strands and secondary structures (such as P box) which are mentioned in the manuscript?

2. Part 3.3. GR-LBD - In addition to discussing the detailed residues in this domain, could the author provide more information about its overall structure?

3. Line 192 – It should be “[61]”, not “[61”.

Author Response

Point 1. I appreciate the reviewer for highlighting this point and changes have been made to Figures 2 and 3 to include the additional labels requested and the figure legends have also been updated where necessary.

Point 2. I agree the description of the GR-LBD was a little inconsistent in terms of detail. The structure of this section has been modified and a more general information has been included on the overall structure.

 Point 3. Corrected.

Reviewer 3 Report

The only comment of the reviewer pertains to this article's title. Since this work is honed on Prof Gustaffson's work - and is part of his festschrift - this could/should be stated in the title.

Author Response

I agree the original title was too broad and this has been modified to better reflect the content of the article. I make clear in the abstract that the focus is primarily on the work from Prof Gustafsson and colleagues, so don’t feel this needs to be repeated in the title itself.

Round 2

Reviewer 1 Report

Accept in present form

Reviewer 2 Report

All questions have been answered and the manuscript has been modified.
There are no other comments for the authors.