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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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?

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.