Protein Malfunction and Disease: Making a Sickle Cell Mutation

(Teacher version)

Scientist know that Sickle Cell Disease is an example of a disorder caused by mutation in the DNA. The result of the mutation is a misshaped protein that includes a replacement of a hydrophilic glutamic Acid (E) for hydrophobic valine (V). In this activity you will look at the amino acid change and determine the molecular basis for the disease that lies in the DNA. You will then be asked to relate the change in the protein to the implications for the health of the individual that has the mutation.

The molecular defect that causes Sickle Cell Anemia can be only ONE amino acid, although the full hemoglobin complex is over 574 amino acids long! You can model the effect of one amino acid change by making the critical piece of hemoglobin.

A model of the critical hemoglobin fragment in the red blood cell of a normal person.

Open the Molecular Workbench: hemoglobin [http://xeon.concord.org/webstart/jnlpFiles/modelerPages/hemoglobin.jnlp].

1. Build a string modeling the hemoglobin fragment of a normal person with the following amino acids: val-his-leu-thr-pro-glu-glu-lys-ser-ala-val-thr-ala-leu-trp-gly-lys-val-asn-val.

2. Run the model

3. Draw a picture of the resulting shape of the chain in the space below.

(There could be variations, especially left-right reversals, of this model.)

4. Build a model of the critical hemoglobin fragment from someone with Sickle Cell Anemia by clicking on glutamic acid and replacing it with valine.

 

 

 

5. Draw a picture of the shape of the chain in the space below.

6. Look at the DNA code. What is the difference between the DNA codons for normal hemoglobin and one for sickling hemoglobin?
The sixth codon for normal hemoglobin is GAA.
The sixth codon for sickling hemoglobin is GTA.

 

7. Explain how this substitution in the genetic code affects the shape of the proteins produced. Include the steps of protein synthesis in your description.
The substitution of the T nucleotide for the A nucleotide changed the way the codon was transcribed. The wrong amino acid was placed in the protein chain causing a different shape structure of the protein. In this case, the substitution was a critical substitution and caused a significant change in the structure of the protein.