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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:
A. Hydrophobic (non polar)
amino acids will be buried
inside the globular protein
where they are away from
the water molecules that
surround everything in a cell
(indicated by the amino
acids inside the circle.
B. Charged amino acids will
be on the surface of the
protein where they often
neutralize each other and
form an electric bond (slat
bridges)
C. Hydrophilic amino
acids will be on the surface
of the protein where they
can interact with water by
forming hydrogen bonds
D. Cysteine amino
acids often interact
with each other to
covalent disulfide
bonds that stabilize the
protein structure
E. When completed sketch a diagram of the structure you made. Use colored pencils to indicate
the different colors of the tacks. This is the tertiary structure of the protein.
F. What happened as you continued to fold your protein?
G. Were you able to fold your protein so that all of the chemical properties were in effect at the
same time? Explain
H. If not, can you explain why you were not able to fold your protein so that all of the chemical
properties were satisfied?
I. Then compare your structure with the structure made another group. What similarities do
you see? List them below.
J. List the differences. How do you explain the differences you observed?
K. 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.
L. Compare this structure in K with the original structure you drew in E 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.)
Complete the questions below for HW:
M. How many different proteins 15 amino acids long can you make, given an unlimited amount
of the 20 amino acids that exist in nature?
N. Most real proteins are actually around 300 amino acids long. How many different proteins,
300 amino acids in length, could exist?
O. Research – how many proteins are found in the human body?
P. Why do you think that there are fewer actual proteins than possible ones?
Q. As you know, proteins are critical to your growth and well-being. In fact, life cannot exist
without proteins. List some important proteins and the functions it performs in your body.
R. 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.
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?