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Activity 2 Worksheet

HOW A PROTEIN GETS ITS SHAPE: RESPONDING TO WATER OR LIPIDS
Teacher version

Why is understanding protein shape important? Understanding how a protein folds into a specific shape is one of the most important and challenging problems of modern science. If we could predict how a particular sequence of amino acids would fold, we could build protein-based molecular machines similar to those found in a cell. For example, if we understood the way a misfolded protein is responsible for a serious illness, we could probably design the right medicine to help those with the illness.

Why should we use the Folding Polymer model, with its water and oil? Every protein in a living cell is surrounded by water or by lipids. The surrounding plays a very important role in the shaping of a protein. To explore the role of the surrounding water or lipids on protein folding, we will work with a dynamic model of a string of beads surrounded by either water or lipids (oil). Every "bead" in the string represents an amino acid, all beads are linked to each other with covalent bonds, and the whole string represents a fragment of a protein, such as a hemoglobin fragment or a piece of bee venom's protein, or some other cellular component or machine. Working with the dynamic model, we will explore how water or lipids affects the folding of the protein chain. We will investigate the role of different amino acids in this process and find out how the changes in their sequence within a protein chain can affect the shape of a folding protein.

What is the effect of placing a protein chain in different environments?

For a amino acid to become part of a protein, it should have at least two covalent bonds to connect it to its neighbors. When amino acids are linked in a protein chain, the amino group and carboxyl group are bonded or "taken." The key part of the amino acid that is left to interact with water is the group of atoms we call a side-chain, residue or radical. Let's find out more about the side-chains and their response to water.

 

A. Water and Oil - What's the difference to a protein?

Vacuum Run

1. Open the Folding Polymer Model, a protein made only of alanine amino acids. [http://xeon.concord.org:8080/modeler/webstart/protein/ala20.jnlp] the model may take a while to start.

2. Make sure the "Select a solvent type" is set to "Vacuum."

3. Click the "Run" button, and observe what happens to the polymer chain. Describe and draw what you see here.

Water Run

4. Set the "Select a solvent type" window to "Water."

5. Click the "Run" button, and observe what happens to the polymer chain. Describe and draw what you see here.

 

 

6. What is the property of alanine that helps explain its reaction to water?

Alanine has no charge (is neutral), is non-polar and hydrophobic. You should see the chain of alanine amino acids folding into a ball. They look as though they are trying to stick to each other. The polar water molecules make hydrogen bonds with as many other water molecules as they can. Since water cannot bond with non-polar alanine, these amino acids are pushed towards each other.

 

Oil Run

7. At the "Select a solvent type" window, this time choose "Oil." Click on the "Run" button, and describe and draw what happens to the polymer chain.

The tightly wound ball, when placed in oil, unwinds.

 

8. Compare the reaction of protein to water and to oil.

While the protein is in water, water repels every hydrophobic alanine amino acid, so the chain can only wind into a ball. In oil, on the other hand, every alanine in the chain is attracted by the surrounding molecules of oil, a process similar to dissolving. The attractive forces act from all directions equally and the alanine chain is free to float. The chain unwinds.

 


B. What is the effect on the shape of a polymer chain of replacing just a single amino acid "bead"?

1. Before starting: make sure the "Select a solvent type" window shows "Water".

2. This time, change the first amino acid from alanine to glutamic acid, and run. Draw what you observe.

 

3. Now change the first two and last two alanine amino acids to glutamic acid and run. Draw what you observe.

 

4. Explain how just a change of one or two amino acids have such an effect.

The new, replacement amino acids are 'hydrophilic;" they have side chains that are attracted to water. They "pull' the chain out into the water where it can make as many hydrogen bonds as possible.

 

C. What happens when a part of a polymer chain is water-fearing and another part is water-loving (and visa versa)?

1. Make sure the "Select a solvent type" window shows "Water", and not "Vacuum" or "Oil".

2. Build a polymer chain with a set of 10 hydrophilic amino acids next to each other in the middle of the chain. Run the model.

3. Describe and draw what happens to the shape of the protein.

The model will assume the shape of a hill or dent.

4. The drawing below represents a whole protein in water.

Where would you expect to find water-fearing, hydrophobic amino acids, at locations A, B or C?

 

Location __B___

 

Why?

Hydrophobic amino acids are pushed away by water outside the protein. Water preferentially makes hydrogen bonds with other water molecules more than with those amino acids that are neutral.

 

 



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