Biology basics: Protein folding

Protein folding is a fascinating area of science for several reasons. Understanding protein folding may well open up the path to find cure to the diseases that arise from incorrect folding. Also, programming and algorithms have not been all that successful in predicting how a protein will form.

Biology basics: Proteins

Proteins are present in biology everywhere. Without we wouldn't exist. Nor would bacteria, fungi, viruses, pet dogs and our gold fishes..... Proteins are essential to all forms of life and this is why it is important to understand them.

What is a protein?

Proteins are long molecules that consist of reoccurring subunits called amino acids. Proteins are needed for our bodies and the cells in our bodies to function properly. Our body structures: cells, tissues and organs cannot exist without proteins.

Enzymes, many hormones and antibodies that we hear about are proteins. Hemoglobin which carries oxygen in the blood are also proteins. Many neurotrasmitters, involved in the transmission of messages between nerve cells, are also proteins.

Almost every biological process involves, in one way or another, proteins. Examples of the functions of proteins in the human body are:

• Enzymes which makes biochemical reactions occur faster
• As antibodies for our immune system
• As hormones, which help cells signal between each other and coordinate events in the body (such as menstruation in females.
• The hemoglobin protein transports oxygen through the blood.
• The rhodopsin is a protein in the eye is vital for vision
• Muscle contractions involves two types of proteins (actin and myosin) are involved in muscle contraction and movement.

What are amino acids?

These 20 amino acids are make up proteins can be arranged in many different ways to create millions of different proteins, each one with a specific shape and specialised function in the body. Anfinsen showed that the sequence of amino acids (primary structure) was what determined the final shape of the protein. The twenty amino acids are:

• Alanine
• Arginine
• Asparagine
• Aspartate
• Cysteine
• Glutamate
• Glutamine
• Glycine
• Histidine
• Isoleucine
• Leucine
• Lysine
• Methionine
• Phenylalanine
• Proline
• Serine
• Threonine
• Tryptophan
• Tyrosine
• Valine

How proteins fold?

Proteins need to fold into specific three-dimensional shapes to work properly. Anfinsen's experiment showed that many proteins can fold without help. Some proteins can still need a bit of help from special proteins called chaperones. These protein separate the folding protein from other cellular components so the protein can fold in peace, without being disrupted by multitude of other things present in the cell. To get a feel of how proteins fold, have a look at the video below that shows a protein folding.

This simulation requires lots and lots of computational power. The simulation was made possible with folding@home, where more than 280,000 people all around the world donated unused computer power (when their computer was idling). Protein folding is very sophisticated and often does require the combined power of 280,000 to model.

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From their website:

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Get support, join a team, and learn how your computer and (as of today) 281,427 others contribute to finding cures for some of life’s most threatening illnesses.

Visit their site at http://folding.stanford.edu/. I think it's a lovely movement. Hundreds of thousands of people uniting to fight disease. Sounds incredible, doesn't it?

CiPS cells- stem cells created using chemical alone

Hongkui Deng, a stem-cell researcher at Peking University in Beijing has reported being successful in generating stem cells without the addition of extra genes, which previously had not been possible. 

The idea of induced pluripotent stem cells (iPS cells) has always been appealing. Induced pluripotent stem cells would have a large clinical potential, especially by allowing the growth of replacement cells and tissues for a patient, without the fear of rejection. After all, cells generated in this way should be very similar, if not, identical to the patients own cells. For example, a patient could have specific stem cells generated from their skin cells. It could be turned into brain cells that can be transplanted into their body, possibly curing brain ailments.

So what exactly is a pluripotent stem cell?

Pluripotent stem cells are cells capable of giving rise to all the tissue types in the body. The stem cells in embryos are pluripotent. Some of its medical applications are obvious. It allows scientists to make brain, liver, heart, muscle and other tissues that is specific to an individual or organism.

Two researchers from Kyoto University have previously discovered that four genes could reprogram adult mouse cells in 2006¹. Adding the genes into the cell (using viral vectors- molecular biology tools developed from viruses) could reprogram the cell into a pluripotent stem cell. Pluripotent stem cells made in this way are called induced pluripotent stem cells (iPS cells).

So what's so new about this discovery?

Like previously said before, the generation of pluripotent stem cells has been shown to be possible even since 2006. However, introducing extra genes into cells could increase the chance of undesired mutations and, of course, cancer. The new aspect of the discovery is that pluripotent stem cells can now be generated without risk of mutations and cancer. This can open up the path to therapies that do not risk generating dangerous mutations.   

From the original article²

Pluripotent stem cells can be induced from somatic cells, providing an unlimited cell resource, with potential for studying disease and use in regenerative medicine... This chemical reprogramming strategy has potential use in generating functional desirable cell types for clinical applications. (Abridged abstract of article)

CiPS... sounds promising. It sure does. Keep in tune to see how this will revolutionize medicine and research. 

References

1. Takahashi, K. & Yamanaka, S. Cell 126, 663-676 (2006).

2. "Pluripotent Stem Cells Induced from Mouse Somatic Cells by Small-Molecule Compounds"; Pingping Hou, Yanqin Li, Xu Zhang, Chun Liu, Jingyang Guan, Honggang Li, Ting Zhao, Junqing Ye, Weifeng Yang, Kang Liu, Jian Ge, Jun Xu, Qiang Zhang, Yang Zhao, and Hongkui Deng; Science 1239278, published online 18 July 2013; DOI:10.1126/science.1239278; Link to Abstract

Classic Experiment: Anfinsen's Experiment

The focus of this post is not to talk about much new science. Instead, it is to commemorate one of the classic experiments of biology, namely, Anfinsen's experiment. Anfinsen's experiment was an experiment that allowed scientists to conclude that the 3 dimensional structure of a protein was controlled by primary structure of the protein.

Most proteins have a elaborate 3-dimensional structure for it to properly work.  An example would be the structure of DNA ligase, a protein that can join 2 bits of DNA together. 

If DNA ligase did not have this structure, it probably would not function properly. But how does DNA ligase know to assume this structure? What Anfinsen showed was that the DNA ligase itself knew that it had to assume this structure. 

How did it know it had to assume this structure? It just does. In the future, we may examine protein folding mechanics, but for now, let's just leave it here. 

How did Anfinsen showed that the final form of the protein could be obtained without help from other components in the cell. He took a protein called ribonuclease and unfolded it (using chemicals called urea and beta-mercaptoethanol)

Then Anfinsen removed the urea and beta-mercaptoethanol. He then left unfolded ribonuclease alone and the next day, ribonuclease refolded again, in solution without the help of other cellular components (such as other proteins).

This showed that the primary structure of the protein, just the sequence of amino acids, has enough information to determine the final three-dimensional structure. This was a very significant discovery that led Anfinsen to receive the 1972 Nobel Prize in Chemistry, along with Stanford Moore and William H. Stein. 

For further information, check out the link to the Nobel Prize in Chemistry. Also, if you are interested, check out these two books. The first book, Biology: Concepts and Connections, is a very well written general biology book that is has a nice introduction to protein biology. The second book is a more advanced book on protein biology. 

Are women more empathetic than men?

"Are women more empathetic than men?" 

"Are females more caring than males?"

"Girls are more caring than guys?"

These are all common ways of wording an interesting question that has been a minor debate for quite a while. But, amazingly, there has been scientific evidence backing this claim. It is also suggest that men are more likely to desire revenge more than women. Let's look at the psychology of empathy.

[This article is looks at the results of Singer et al. (2006) results, see article links later in the article for more details]

Specific parts of the brain become active when an individual feels empathy, as shown below. Other parts of the brain turn on when a person is psychologically rewarded (and as a result and feels better)

Scientists by using this method can infer how a person is feeling. Now, we play the Ultimatum game. Basically, the gist of the game is a follows:

• A participant plays the Ultimatum game with two other people, who are supposedly also "participants". Little does he or she know that they are actors hired for the experiment.
• One actor, Actor A, is fair to the participant. With the money he or she receives, they split it evenly with the participant. 
• One actor, Actor B, is unfair to the participant. With the money they receive, he splits it unfairly with the participant. (For example, Actor B gets $100 which the participant knows about and says "Hey, I'll offer you $20.")

As a result, the expected result would be the participant likes Actor A and dislikes Actor B. The participant then sits in a MRI machine and watches (possibly through a monitor) Actor A and Actor B receive an electrical shock. Have a look at the results. Here's where things get interesting...

(Reproduced from Singer et al. (2006))

What is observed is that in both men and women feel empathy for the fair player Actor A. Women generally also feel empathy for the unfair player Actor B. Looking at the males, we see that males generally don't feel empathy for the unfair player. In fact, we see something more interesting. Males are psychologically rewarded when the unfair player gets shocked. The parts of their brain that rewards them turns on more often then in women. 

(Reproduced from Singer et al. (2006))

So what does this study suggest exactly.

• Men when treated unfairly feel less empathy for the person that is pass that injustice onto them. 
• Men feel good when people that have treated them unfairly are punished by the heavens
• The same is less true in women

There we have it. Women are more empathetic than men. Men also have a higher desire for revenge than women. We don't know if this is always true since this is a very specific situation, but I can hear the male participants subconsciously cry out "Turn up the voltage!".

"Are men better than women?"... that is a question for another day.

Reference link to Singer's original article.