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Monday, March 26, 2012

BiGCaT: Protein Structure

The last two weeks I have been busy with a course I gave last week (2x two hours lectures, 2x three hours practical) on Protein Structure. I had slides from last year at my disposal, but added some stuff, including a pointer to Google Play's page for the Jmol Android App (cool stuff!). The content involved the basic links between primary, secondary, tertiary, and quarternary structure.

At Maastricht University we use problem-based learning, and the topics for the students of this block (two bachelor studies) were aging and immunology. Interesting, because as a chemist I have limited background in these fields. Other content in this bioinformatics course done by our BiGCaT group involved SNPs, and I found a few interesting examples. As protein structure visualization tool, the course is using Yasara, a great tool, but next year I will prefer to use Bioclipse.

For the aging topic, I found a protein encoded by the WRN gene involved in Werner's Syndrome. I do not believe they found the actual cause of this disease yet, but that just makes it more interesting. The 3AAF structure in the PDB database (which, BTW, gets really slow when the USA wakes up), is associated with two SNPs:


So, it wasn't more than logical that I had the students visualize the residues and ask them to hypothesize which of the two was more likely to affect DNA binding:


Also very interesting to look at in this structure, is the π-π stacking by which this protein structure binds to the DNA:


OK, you really need to look at this yourself in 3D, but you see the Tyr and Phe binding to the DNA bases here :)

So, next year, one of these exercises will basically become a Bioclipse plugin with a nice cheat sheet. I also plan to finally write that plugin that educates people in the Jmol scripting language. Who wants to team up for that?

The other students got to look at the 3O4L structure (thanx to Patrick for the great topic!), which is a beautiful complex of protein structures from a normal cell (green and blue) and a T-cell (yellow and red):


In the middle is a small peptide (element colors), broken down by the normal cell from a Epstein-Barr virus. The membrane-bound protein parts are missing, but if you just imagine two huge cells on the left and right of this!

The red and yellow part are very similar structures, with a really nice S-S bond holding together the two subunits (all S-S bonds are depicted in magenta):


And this simple complex has many variants on the T-cell receptor side, allowing our human body to adapt to all sorts of viruses, etc. This is what life looks like! Isn't chemistry amazing!