Diana’s comment on: Sequence heuristics to encode phase behaviour in intrinsically disordered protein polymers

By Diana Silva Brenes

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Relating molecular structure to function is the first step and one of the greatest challenge to understand nature’s designs or to make novel “functional designs” of our own. This paper by the Chilkoti group begins with statistical analysis of some of the most relevant proteins displaying LCST and UCST behavior. By analyzing the peptide sequences, the authors identify as common motif for both behaviors a high glycine & proline content. Furthermore, for LCST abundance of aromatic residues seems to be a requirement whereas UCST peptides seem to be encoded by a pair of zwitterionic residues.
To test if these observations lead to LCST/UCST phenomena, over 80 model peptides were recombinantly synthesized and their thermoresponsive behavior was measured by UV absorbance while changing the temperature. Each peptide presented the predicted behavior, giving support to their observations. Furthermore, by comparing a few selected examples, they show how an increase in hydrophobicity leads to an increased UCST cloud point and how eliminating one of the residues from azwitterionic pair turns a UCST peptide to an LCST peptide.
The LCST and UCST behavior is, however, a complex phenomenon dependent on protein-protein versus protein-water interactions, which in turn are modulated by more factors aside from the sequence of the protein. The possible scenarios are limitless, and the authors give insight on the most significant: peptide length, concentration, and pH (charge state of protonable atoms).
The robustness of the behavior encoded in the rules they found can be seen by a hybrid peptide containing both an LCST portion and a UCST one. The resulting peptide displays both behaviors, albeit at different temperatures from the “parent” sequences.
Finally, the authors show that searching for the characteristics they determined as important for LCST/UCST behavior throughout the human proteome produces examples of proteins whose function could very well be related to a thermoresponsive behavior, highlighting the applicability of their observations to understand the phenomena that make life as we know it possible.

Quiroz, 2015. Sequence heuristics to encode phase behaviour in intrinsically disordered protein polymers

7 thoughts on “Diana’s comment on: Sequence heuristics to encode phase behaviour in intrinsically disordered protein polymers

  1. Rating (synopsis): 5/5
    Rating (image): 5/5

    Diana’s comment is well written and has a natural flow that I like very much. I really like the first sentence because I feel it ignites the curiosity of the reader (am I the only one?). I shall make an attempt at this in my future comments. In the comment, she could have mentioned what are these “relevant proteins that show LCST behavior.” Nevertheless, that’s just a small detail of this great synopsis.

    The image is a nice cartoon representation of the article and it is very immensely creative. I would have liked to see Kekulé structures of the repetitive units of the polypeptides, but I guess there were too many to choose. Of the two images I like the one with the Math Lab logo on the computer, it was a nice touch.

  2. Rating (synopsis): (5/5)
    Rating (figure): (5/5)

    The article that Diana presented was very interesting because, as they say, the structure determines the function. As Diana mentioned and showed in the synopsis, the authors of the article presented evidence of that statement. Again, the concept of LCST as an important factor and now another concept which is the UCST. In general, Diana did a very good summary of what the article was about. She used a simple vocabulary that I could understand and I found interesting since I could relate it to my biochemistry class.

    The image was very creative and constructive. It showed the essence of the article. The image contributed to my understanding of the article.

  3. Rating Synopsis: 5/5
    Rating Figure: 5/5

    It was really interesting how they studied the phenomenons of LCST and UCST. Specially because I had only so far known a bit about the LCST. Also it was really fascinating how they go through all that work of synthesizing 80 models of peptides and study them to exposed in a more concrete way the relationship between structure and function. This synopsis was really good written and straight forward with what it was obtained from the research done.
    The video/figure is really cute and creative. Also it is a really good representation of the synopsis already presented.

  4. Rating Synopsis: 5/5
    Rating Figure: 4/5

    The synopsis is great, in my opinion, because this article is plagued with experiments and results, and summarizing all of that into a few hundred words is extremely difficult. I really liked the laws Diana used for summarizing the results from the paper in the presentation and I wished she would used a similar way of explaining the main results. That’s just a personal preference, and maybe she did not do it, because that style fitted the presentation better. As I mentioned to Diana this paper reminds me of Sieve theory and it really helped to understand the power of the heuristic method used throughout the article.

    For the figures I feel like I have to disagree with my colleagues who praised them. The style is very Diana-like and gives a fun look into the article without overwhelming the audience. However, I thought the idea was to practice Table of Contents figure-making skills and these are clearly not allowed as part of an article. Apart from that, TOCs have to capture the imagination and these figures do that, while still keeping the core of the idea that the authors had when preparing this article. For this reason I can safely give a 4/5. I feel Diana does not need to practice figure-making skills since I know she has a talent for making these, but I wanted to see how she could have creatively explained the article with a TOC worthy of an article in an important journal.

  5. Rating (synopsis): 5/5
    Rating (figure): 4/5

    Both images are very creative and very flashy but very creative and very flashy. What I mean by this, is that to me is not very clear what these images want to convey the first time that you see them. If you take your time with the images you can follow the rational. Same thing with this article. While reading the article its length and complications makes it a hard read. That’s why I’m actually proud of Diana on taking this article and making an easy to read post. Managing on transmitting the main ideas of the article and summarizing it in a rational based narrative.

  6. Synopsis: 5/5
    Figure: 5/5

    I remember when I saw Diana’s presentation in the group meeting. I thought that the paper had a lot of data and she presented them in an organized way. She also did the same with this synopsis. It was simple and clear. As Luis mentioned, when I started reading the synopsis it cached my attention and ignited my curiosity. Now, regarding the figure, the cartoons explain the main idea of the paper without complicating it too much. I really like the scientist with the different letters that he can choose to do protein sequence and the questions that he is asking himself to study the LCST and UCST behavior of the peptide.

  7. Rating (Synopsis): 5/5
    Rating (Figure): 4/5

    The article presented by Diana was very dense and hard-to-read, but in her presentation at the Group Meeting, she was able to digest the data for us and translate it by presenting it in an organized and simplified manner. However, I remember thinking that it was a lot of data as I read the article and also as I watched Diana’s presentation. I had no doubt that Diana would write a great synopsis that summarizes the article’s main idea and most important findings without including all of the scientific jargon, and she delivered.

    I think that the figures constructed by Diana belong more in a presentation for people who are not experts in the field or in a textbook more than they do in a scientific journal as a TOC figure. Although they illustrate the article’s rationale and flow in a very nice and creative way, I think they could be altered to communicate the research more efficiently.

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