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Activity Overview:
Key concepts:
Amino acids with opposite charges are attracted to each other; those with identical charges are repelled by each other. The interactions between these charged amino acid monomers in the polymer chain help determine the shape of the protein.Students learn about amino acids, their structure and their charge, discovering how differently charged amino acids affect the shape of a model protein fragment. They are introduced to the case of Sickle Cell Anemia, and begin their exploration of its molecular mechanism.
Learning Objectives:
Students will be able to:
Connect the unique component of an amino acid, its side chain, to its charge.
Macro to Micro Connection:
To engage students in a study of the structure-function relationships in proteins, students relate the macroscopic-level symptoms of the disease of Sickle Cell Anemia to the microscopic-level phenomenon of protein charge. To do this, students are asked to reason about the interactions of molecules that underpin the biological phenomena of protein folding and reason about the genetic control of the tertiary structure and function of proteins. This theme is explored over the course of the module.
Conceptual Prologue:
The interaction of charged amino acids with each other is partially responsible for the shape of proteins. Monomers with opposite charges attract each other; those with identical charges repel each other. These forces are in part responsible for "molecular sculpturing." That is why the position of the amino acids in the polymer chain (we call it a "sequence") is important. For example, the closer the amino acids with opposite charges are to each other, the more strongly they interact.
In addition to attracting various parts of the chain by strong electrostatic forces between charged amino acids positioned in these parts of the chain, the weaker hydrogen bonds between polar groups of the neighboring amino acids turn and shape protein chains into spirals or parallel sheets.
The interaction between charged and polar amino acids plays an important role in defining a specific shape of a protein. Generally speaking, for every sequence of amino acids (also called primary structure), we should expect a differently shaped protein. Such variety is important for cell functioning.
Activity Design and Execution: Major Science Concepts Structure and property of amino acid, charge, primary structure of proteins Assumed Previous Knowledge: Cell parts, cell function, macromolecules, atoms, molecules, polarity Time: 1-2 50-minute classes Technology Requirements: There is one model in this activity, which can be launched in one of two ways:
1. From your browser. Click the link below.
Molecular Workbench:"Protein Folding: Alanine Only " model http://xeon.concord.org:8080/modeler/webstart/protein/ala20.jnlp2. By going through the Molecular Workbench application on your computer (workbench.jar). Then you should click the following links: Student Pages, Protein Folding, A Polymer with 20 Alanines.
It may take a short while to launch the Molecular Workbench the first time.
Supportive Materials: *The Case of Sickle Cell Anemia [PDF version]
*The Structure of Amino Acids in Proteins [PDF version]
*A Chart of Amino Acids [PDF version]
*Worksheet: Amino Acid and Charge (Student) [PDF version]
*Worksheet: Amino Acid and Charge (Teacher)(Homework for next activity) *How do Amino Acids React to Water and Oil? [PDF version]
Advanced preparation: Print or bookmark support materials
Prepare model for access (See above)
Visit and bookmark Student Index
Investigative Question: How can replacing one amino acid in a protein chain cause a disease?
Steps
Administer the Pretest [PDF version], if they have not already taken it.
Have students read The Case of Sickle Cell Anemia. In this case study, students are introduced to some of the key investigators of the disease that affects one of the most important molecular machines, hemoglobin. They will be engaged in determining why such a small variation in the amino acid sequence of a protein can make a difference in its function. Students will revisit the Sickle Cell Anemia story in the activities that follow. At the end of this unit they will be building and investigating a fragment of hemoglobin using the modeling software.
2. Structure of Amino Acids. Review The Structure of Amino Acids in Proteins with your students and look at the Chart of Amino Acids. It is important for students to be able to identify the amino group and the carboxyl group, be comfortable with how amino acids form peptide chains and how the side chains are responsible for specific properties.
Emphasize: All amino acids have an amino group (NH2), a carboxyl group (COOH), and a hydrogen (H) linked to the central carbon (C) atom. The presence of the carboxyl (COOH) group makes any organic molecule an acid, as in "amino acid." The side chains, which are the unique parts of amino acids, give the amino acids their special characteristics.
A. How could a difference in amino acids result in a disease?
B. Look at the molecular structure of glutamic acid and valine. Can you find any differences in their formulas?
C. What are the properties of the original amino acid in hemoglobin? What are the properties of the substituted amino acid in Sickle Cell hemoglobin? (Check the Chart of Amino Acids)
Develop a hypothesis about how these properties might affect the shape of the protein hemoglobin.4. How Does Charge Affect the Shape of a Protein? Introduce the Molecular Workbench software to the students. Explain that this software is designed to help them observe the behavior of amino acids. Have students bring up the Molecular Workbench software. (See Technical Note in table above,)
Discuss with students that this is a dynamic model, which means that it is not an animation. In fractions of seconds, the computer is actually doing millions of calculations, displaying the movement and positions for all components of the system, factoring in what we know about particles, their energy, the strength of their interactions with each other, with oil or water. During this activity students will be looking at a protein chain in a vacuum and studying the effects of charge and sequence on the shape of amino acids. It is important to help students think about both, the role of charge and the role of the sequence of charges (their positions in the chain) on the resulting shape of a protein.
It may be best to have students present their sequences to the class and show the resulting shapes. This will help guide the discussion about the role of charge and sequence.
Distribute the Amino Acids and Charge Worksheet.
5. Transition to next activity. Have your students anticipate what effect water might have on the shape of proteins. (A cell is mostly water, after all. Are there charges on water molecules?)
6. Distribute homework for the next activity: How do Amino Acids React to Water and Oil?
Extensions
Explore amino acids that build disulfide (S-S) bonds. Sulfur (S) containing amino acids, such as cysteine and methionine, located in the different parts of the protein chain, interact with each other, making covalent bonds that link two different parts of a protein molecule together, and often form loops in the otherwise straight chain. Every S-S bond made between two cystein molecules serves as a "staple" holding the shape in a more steady position. This S-S covalent bond is not as strong as the peptide bond between amino acids, and breaks when heated at a temperature much lower than that required to break the peptide bonds making the protein chain.
Go to our Molecular Viewer [http://www.concord.org/~dima/jws/pdbviewer/index.html] and look at the amino acids glutamic acid and valine. This requires MAC OS 10.2 or higher, and recent PCs with graphic accelerator cards.
Visit Citilab: The Mystery of the Crooked Cell, [http://www.bumc.bu.edu/Departments/PageMain.asp?Page=7355&DepartmentID=285] , a laboratory on Sickle Cell Anemia.
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