BIOC 223

Last weekend, I attended a session from TEDxWellesleyCollege and was able to listen to Janet Iwasa, a fellow biochemist, along with a few other amazing speakers. Janet Iwasa is a molecular animator, and works to create scientifically accurate animations in order to visualize cellular and molecular processes for communication between scientists and to the general public, and also as a way of interpreting large datasets in a more understandable way. I thought you all might especially appreciate her animations of hemoglobin alternating from an oxygenated to deoxygenated form!

http://biochem.web.utah.edu/iwasa/projects/hemoglobin.html

While PyMOL is great for visualizing proteins, it doesn’t allow us to visualize changing protein conformations the way these animations do.

This week, we had the opportunity to work with the model kits to see how proteins are structured and with the noodles to make the proteins ourselves. I think that now I have a better idea of how mutations affect proteins and their function because their structures can be altered if the amino substitution is significantly different. It is this reason that even if it is a one amino acid substitution, like in sickle cell, where the glutamic acid residue is replaced by valine, it can cause red blood cells to assume abnormal shapes.  Using the hands on models helps me visualize how protein structure can change accordingly from just the primary sequence.

So, I was walking around CVS in the ville the other day while running some errands, when I stumbled across this:

They were being marketed as “Youth and Diet pills”, and they really got me thinking about the way scientific ideas are presented in the popular media. I’m an unashamed consumer of trashy magazines, and I’ve recently noticed an uptick in the amount of “scientific” coverage in a lot of womens magazines. Most often, these scientific articles are popular pieces reporting on the latest and greatest technological breakthrough that can help women get their hottest beach body ever.

With that in mind, I thought it was really interesting how the packaging for these pills highlighted the inclusion of collagen and amino acids, as if we should immediately be reassured of the pills’ efficacy by the presence of science-y sounding terms. I’m pretty fascinated by the science behind a lot of mundane items, such as shampoo and diet pills, but I’m not such a fan of the way scientific research is often portrayed by the media. It seems like either scientific concepts are a “black box” that normal people aren’t expected to understand, or science is the enemy (see: mass hysteria over “chemicals” in everyday products, even though everything is made up of chemicals).

Collagen is a term thrown around in the media a lot, usually in the form of celebrity plastic-surgery exposes. The pills shown above are capitalizing on the term’s popularity, although I’m skeptical about the “Youth and Diet” enhancing effects. But, who knows? We’ve been talking about collagen in class recently, but we haven’t quite discussed all of collagen’s functions in the body. I’m looking forward to learning more about the functions of fibrous-type proteins such as collagen; maybe there really is some effect (again, I doubt it).

I guess what I’m trying to convey is how excited I am that the concepts I’m learning in class are becoming more visible in my everyday life, even if they are coming in the form of cheap diet pills. I think it’s important to fight the way the media tends to portray scientific research, and biochem is helping me get there.

Talking about viral protein coats in class reminded me of the recent end to a band on Italian cured meat. Since the mid 1970s, the U.S.D.A. has been banning the import of non seasoned or cooked hams because of concerns about swine vesicular disease (SVDV). This virus is particularly problematic because it is unusually resistant to heat. X-ray crystallography of the capsid showed that in SVDV there is an increase in ions along the awes where the five structural proteins connect. Additionally, the hydrophobic pocket in the ß-barel of the protein VP1 is larger than in similar strains, which could allow for the binding of different pocket factors that increase stabilization of the capsid.

SVDV capsid

Image from Fry et al. 2003 showing the structure of the SVDV capsid showing the four different structural proteins (VP1,2,3, and 4).

In our last class, we were talking about how viruses take advantage of repeated noncovalent interactions to become incredibly stable, making it very difficult to eradicate them from the body. This sounded perfectly horrible, so I thought I’d share an example of when this can actually be a great thing!

Foot-and-mouth disease (FMD) had a major outbreak among farm animals in the UK in 2001, creating huge loss in food production and major economic losses. So, farmers in the UK hoped to vaccinate their livestock to prevent future losses. However, existing vaccines are very unstable, resulting in limited shelf-lives and high expenses due to the need to use a cold-supply chain (they denature at room temperatures, and a ph<7.0).

So, researchers decided to actually alter the virus genome, changing the structure by one amino acid (one histidine was converted to a cysteine, creating a sulfide bond). This greatly improved the stability, and allowed them to (successfully) use the empty capsid of FMD as a vaccine in cattle.

So, sometimes virus’ incredibly stable structures can actually be used against them!

I remember Professor Didem mentioning early in our introduction to amino acids, that certain amino acids are endogenous in humans, while there are some that must be consumed from other sources. I’ve heard this before as well, and I’ve begun wondering about what makes these endogenous amino acids (often called “nonessential” amino acids) different from the “essential” amino acids. So I decided to do a bit of research!

There are 9 essential amino acids (phenylalanine, valine, threonine, tryptophan, methionine, leucine, isoleucine, lysine, and histidine), and an additional three for infants and growing children (cystein, tyrosine, and arginine). Interestingly enough, all of the adult amino acids could be supplied by eating eggs or soy protein (as in, eggs and soy protein both contain all of these essential amino acids).

While there is no obvious pattern among these amino acids, except that all of the aromatic amino acids are essential for children, the main difference is that the nonessential amino acids can be synthesised from other biological substrates, while the other amino acids cannot. For example, alanine can be synthesized from many other amino acids. To complicate this a bit more, a few of the essential amino acids are easily converted to each other (ex.phenylalanine and tyrosine), so only a diet including one of these amino acids is truly essential.

Since the body does not store amino acids for later use, as it does with lipids and carbohydrates, lacking only one amino acid could result in muscle degradation, or degradation of other protein structure; experiments on healthy male graduate students (of course they were grad students :]) also showed that lack of certain essential amino acids resulted in symptoms of nervousness, exhaustion, and dizziness (http://www.jbc.org/content/193/2/605.full.pdf). So, lesson learned – eat your protein (esp. eggs)!

My friend, who is allergic to gluten, was eating a gluten-free brownie. I was curious about the purpose of gluten in baking, and after a bit of research, found that gluten is actually a protein complex! While the exact structure of gluten is not well characterized, it consists of mostly of gliadin, which is a globular protein molecule, and the more linear glutenin. The main cause of these different structures is actually that gliadin disulfide linkages are primarily intra-molecular, causing them to become more compact, while glutenin proteins interact through both intra- and inter-molecular disulfide linkages! These differences in tertiary structures of course must trace back to their primary structures.

The most interesting part about this is that flour is actually made up of gliadin and glutenin, but they don’t interact until water is added – just another reason it’s so important to consider the environment when considering non-covalent interactions.