Concluding lesson
Student manual
What kind of protein are you?
(Basic)
Student manual What kind of protein are you? (Basic)
Part 1
The hereditary material of an organism is stored in a coded way on the DNA. This code consists of
four different nucleotides: adenosine (A), cytosine (C), guanine (G) and thymine (T). In the case of
RNA, thymine is replaced by uracil (U). The order in which these nucleotides are linked is called a
sequence. Groups of three nucleotides that are next to each other in the sequence are called codons.
These codons can be translated into amino acids. But what happens when something changes in the
sequence, added or removed? This is called a mutation.
There are different kinds of mutations of which five are described below.
Missense mutation
In a missense mutation 1 nucleotide in a codon changes, which can lead to a completely different
amino acid. A missing mutation is a point mutation.
Example of a disease: Sickle-cell disease (http://en.wikipedia.org/wiki/Sickle-cell_disease)
Nonsense mutation
The nonsense mutation changes a codon in the sequence of one amino acid into a STOP codon
(TAA, TGA, TAG). This causes the cell to stop the addition of more amino acids to the protein.
This point mutation finally causes the protein to be shorter.
Example of a disease: Thalassemia (http://en.wikipedia.org/wiki/Thalassemia)
Silent mutation
A silent mutation changes a codon of a amino acid into another codon but does not change the amino
acid. There is most of the time more then one codon that codes for one amino acid. So sometimes a
small change in the DNA sequence has no effect on how a protein is formed. This is why it is called a
silent mutation.
Deletion mutation
The deletion mutation removes a part of the DNA sequence. Due to the fact that the DNA codes is
read in groups of three nucleotides, the deletion mutation also changes the manner of reading the rest
of the sequence.
Example of a disease: Cystic fibrosis (http://en.wikipedia.org/wiki/Cystic_fibrosis)
Insertion mutation
An insertion mutation adds a nucleotide to the DNA sequence. Here too, this has an effect on the
groups of three that are formed and therefore the DNA code will be read differently.
Example of a disease: Huntington‟s disease (http://en.wikipedia.org/wiki/Huntington%27s_disease)
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Student manual What kind of protein are you? (Basic)
Exercise 1
To gain a better insight in the different mutations one can use the mighty mutation maker. In order to
use this program follow the steps below.

Go to http://nature.ca/genome/04/0413_e.cfm#010

Enter your name and click on “decode”.

On the left you will see the different mutations.
Exercise 1.1
Click on the missense mutation. What happens to your name?
Fill in the result in scheme 1.
Exercise 1.2
Click on the nonsense mutation. What happens to your name?
Fill in the result in scheme 1.
Exercise 1.3
Click on the silent mutation. What happens to your name?
Fill in the result in scheme 1.
Exercise 1.4
Click on the deletion mutation. What happens to your name?
Fill in the result in scheme 1.
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Student manual What kind of protein are you? (Basic)
Exercise 1.5
Click on the insertion mutation. What happens to your name?
Fill in the result in scheme 1.
Exercise 1.6
Do you still recognize your name after all these different mutations?
Scheme 1:
Name
Result missense mutation
Result nonsense mutation
Result silent mutation
Result deletion mutation
Result insertion mutation
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Student manual What kind of protein are you? (Basic)
Part 2
DNA can be translated into amino acids. Amino acids then code for proteins. Different mutations can
occur in the DNA that can have effects on the proteins. Five different mutations are missense,
nonsense, silent, deletion and insertion mutations. The effects of these mutations are clearly visible on
the level of DNA (see Part 1). The effect on the protein sequence is more difficult. This part is very
interesting for scientific research, because a disturbed protein function can lead to a wide variety of
diseases like Cystic Fibrosis and Alzheimer‟s disease.
Figure 1. Representation of DNA. The DNA consists of genes. These genes code for the amino acid sequence.
Amino acid sequences can be transcribed into mRNA. mRNA can be translated by ribosomes that connects
amino acids and thereby makes the protein.
The shape of a protein after folding is very important for a protein and its function. This is comparable
with the specific shape of a key to fit into a lock. If the key does not fit, the lock won‟t open. The same
goes for proteins; if a protein does not fit into a receptor, there will be no signal transduction.
To see how proteins are represented in order to do research, you can look at the following movie:
http://www.youtube.com/watch?v=iaHHgEoa2c8
But how do you discover how a proteins folds and what its final shape will look like? Then what are the
consequences of mutations in the DNA for the shape of the protein?
Now make exercise 2.
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Student manual What kind of protein are you? (Basic)
Exercise 2
To go a step further, you are now going to look at the
consequences of mutations for protein folding and the threedimensional structure of a protein. In order to do so, follow
the steps below.

Make a group of 3 or 4 students

Connect the names (first name and surname) of the
people in your group

Translate the names into an amino acid sequence by
using the amino acid alphabet on the right

Go to http://ffas.burnham.org/XtalPred-cgi/xtal.pl

Begin with:
>groupname

Press Enter

On the second line enter the amino acid sequence
translation of the names as depicted in the print screen at
the bottom of this page

Check the „Server Policy‟ box

Click on Submit
Alphabet
A
B
C
D
E
F
G
H
I
J
K
L
M
N
O
P
Q
R
S
T
U
V
W
X
Y
Z
Amino acid
Alanine
Alanine
Cysteine
Aspatic acid
Glutamic acid
Phenylalanine
Glycine
Histidine
Isoleucine
Isoleucine
Lysine
Leucine
Methionine
Asparagine
Asparagine
Proline
Glutamine
Arginine
Serine
Threonine
Threonine
Valine
Tryptophan
Tryptophan
Tyrosine
Tyrosine
Code
A
A
C
D
E
F
G
H
I
I
K
L
M
N
N
P
Q
R
S
T
T
V
W
W
Y
Y
>groupname
Amino acid
sequence
Check box
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Student manual What kind of protein are you? (Basic)
The screen will refresh several times until the calculations are done. This might take a few minutes.
You can also manually refresh the page.

Click on the name of the group when the program is ready. You can find it under “Target id”
(see the screenshot below).
Click

Scroll down and make the questions below.
Exercise 2.1
Which domains are present in your protein “groupname”? (Hint: look at the legend)
The different domains of a protein all have a certain shape. There is a loop form, a helix (α-helix) with
the shape of a spiral staircase and the strand (β-sheet) that looks like a flat plate. The transmembrane
helices are special because the protein crosses a cellular membrane. The amino acid sequence of
your names determines which domains are present in the protein. What might happen when mutations
occur in your name?
In order to check the effect of mutations on your protein you are going to test some different mutations
on it.
Exercise 2.2
Remove the first two letters from each name. What is left of the domains?
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Student manual What kind of protein are you? (Basic)
Exercise 2.3
Remove all the vowels. What is left of the domains?
Exercise 2.4
Insert in 5 randomly chosen different places a “p” (amino acid proline). What happens now with the
domains?
Exercise 2.5
Finally, insert the name of your teacher at a random position. Does this improve the domain structures
or not?
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