Name Date Period Modeling Protein Folding Draw how two amino acids form the peptide bond. Draw in the space below: What we are doing today: The core idea in life sciences is that there is a fundamental relationship between the biological structure and the function it must perform. In this activity we will explore how the structure of the protein that is indicated by its sequence of amino acid is related to its function. 1. Each protein is made up of building blocks or called. 2. Each amino acid is made up of four parts. List them below 3. Which of these are common to all amino acids? 4. Which is unique to each amino acid? 5. How many kinds of amino acids are there? Based on the properties of the R groups or side chains, amino acids could be hydrophobic, hydrophilic, positively charged or negatively charged. Examine the amino acid chart provided and review the properties of the different amino acids. 1. Hydrophobic side chains (R) primarily contain atoms. 2. Hydrophilic side chains have various combinations of atoms 3. Acidic side chains contain two atoms. This looks like a carboxylic functional group. 4. Basic side chains contain atoms. This is called the amino functional group. 5. An exception to the above is. What makes this side chain different?
Activity: With 15 tacks and a mini-toober you can explore the principles of chemistry that drive protein folding. Color-coded tacks represent the properties of the amino acids. 1. Select 15 colored tacks according to the list below. 2 dark blue tacks (blue represent basic amino acids, + charge) 2 pink tacks (red represents acidic amino acids, - charge) 6 purple tacks (hydrophobic non polar amino acids) 3 white tacks (hydrophilic polar amino acids) 2 green tacks (cysteine amino acids) 2. Place your colored tacks about 3 inches apart on the mini-toober in any order you wish NOTE: As you push the tacks into the mini-toober they may hit the wire in the middle and not go in all the way. Reposition the tack so it goes slightly above or below the wire. Be careful not to push the tack through to the other side of the mini-toober where it could poke your finger. Also, be careful and do not tear the foam with the tack. Record the sequence of amino acids or tacks in the space below. This is the primary structure. 3. Now fold your protein following the principles of chemistry as outlined below: When completed sketch a diagram of the structure you made. Use colored pencils to indicate the different colors of the tacks. This is the structure of the protein.
4. Were you able to fold your protein so that all of the chemical properties were in effect at the same time? Explain why or why not. 5. Compare your structure with the structure made another group. What similarities do you see? List them below. 6. List the differences. How do you explain the differences you observed? 7. Now take one of your acidic amino acid and replace it with a hydrophobic amino acid tack. You now have to refold your protein in order to satisfy the chemistry of folding again. Refold your protein and sketch below.
8. Compare this structure with the original structure you drew in 3 above. What are the similarities and differences? (This is a mutation and in a real cell, one difference in amino acid could result in a protein folding so differently that it is not able to perform its function.) 9. Sickle cell anemia is caused by a single change in the amino acid sequence. Amino acid 6 is Glutamic acid in normal hemoglobin. It is replaced with Valine in sickle cell anemia. Using the information you just learned, explain why sickle cell anemia leads to deformed blood cells. 10. How many different proteins 15 amino acids long can you make, given an unlimited amount of the 20 amino acids that exist in nature? 11. Most real proteins are actually around 300 amino acids long. How many different proteins, 300 amino acids in length, could exist? 12. Research how many proteins are found in the human body? 13. Why do you think that there are fewer actual proteins than possible ones? 14. As you know, proteins are critical to your growth and health. In fact, life cannot exist without proteins. List some important proteins and the functions it performs in your body.
Extension and Enrichment: In this exercise you will fold a real protein. You will fold a model of the first of three Zinc fingers of the Zif228 protein. Zinc finger proteins regulate the transcription of DNA into mrnaby binding to DNA and attracting RNA polymerase. A zinc finger protein contains two cysteines and two histidines, which simultaneously bind to a zinc atom. These four amino acids are contained within a 30 amino acid sequence. The primary structure is given below. This time the single letter abbreviations of the amino acids have been used for brevity. Check out the table below The Primary structure of the Zinc Finger protein is: N Terminus - P Y A C P V E S C D R R F S R S D E L T R H I R I H T G C Terminus Amino acid sequence
Map the positions on the Mini-Toober. Since the toober is 48 inches long and the protein has 28 amino acids, each amino acid occupies 1.7 inches on the toober. Use a ruler and measure the distances. Use a pencil and make light marks DO NOT USE A PEN, to mark the distances on the toober. Then add the circled amino acids in the correct positions. Secondary structure: The first 13 amino acids (22 inches from the N terminus) will fold into a 2 stranded beta sheet. This can be done by creating a zigzag structure that is bent in the middle. Hydrogen bonds will keep this structure intact. The last 15 amino acids exist as a compact right handed alpha helix and can be made by wrapping the mini-toober around your finger. Tertiary Structure: Fold the beta sheet and the alpha helix to form the compact tertiary fold of the protein. In its final tertiary structure, the seven amino acids will be positioned such that 1. The two cysteines and the two histidines will be oriented to simultaneously bind to the zinc atom in the center of the structure. Check out the photo on the teachers desk 2. The two hydrophobic side chains of phenylalanine and leucine will be oriented towards the inside of the structure. 3. The positively charged arginine side chain will be exposed to the top of the alpha helix where it is available to bind with the negatively charged phosphate backbone of the DNA Analysis: 1. Both alpha helices and beta sheets are stabilized by hydrogen bonds. Which atoms share the hydrogen in these H bonds? 2. Are these backbone atoms or side chain atoms? 3. Describe the secondary structure of the zinc finger protein. 4. How is the zinc atom involved in the stabilization of the zinc finger protein? 5. Zinc fingers often bind to DNA. How might the Arginine side chain shown in your model be involved in the DNA binding. Hint: What is the property of the Arginine side chain?