Teaching Notes Make a Paper Model: Antibodies (IgG) Overview: In this activity you will make a paper model of an antibody IgG. Learning Goals: 1. Make a 3D model of the antibody using the template(s) provided. 2. Study the 3D model of the antibody to understand its structure and functions. Educational Standards A. Common Core a. Key Ideas and Details i. RST.11-12.3 b. Integration of Knowledge and Ideas i. RI.11-12.7 B. Next Generation Science Standards a. Practices i. 2. Developing and using models b. Crosscutting Concepts i. 3. Scale, proportion and quantity ii. 4. Systems and system models iii. 6. Structure and function c. Disciplinary Core Ideas i. LS1.A: Structure and Function ii. LS1.D: Information Processing iii. PS1.A: Structure and Properties of Matter iv. PS2.B: Types of Interactions C. Advanced Placement Biology - Essential Knowledge (EK), Learning Objectives (LO), Science Practices (SP) a. EK 2.D.4 i. LO 2.29, SP 1.1, 1.2 b. EK 4.A.1 i. LO 4.2, SP 1.3 ii. LO 4.3, SP 6.1, 6.4 c. EK 4.A.2 i. LO 4.4, SP 6.4 ii. LO 4.6, SP 1.4 Teaching Notes 1. It is recommended that you read the Molecule of the Month article on Antibodies before attempting to make the paper model. 2. Follow the instructions for making the antibody molecule. Since the model is quite large it can be made as a group project. Assign each domain (printed on a single sheet of paper) to a different student. The different domains can be put together along with the disulfide linkages as a class/group project. 3. Once the model is made, explore its shape and structure in the context of its functions. Developed as part of the RCSB Collaborative Curriculum Development Program 2015 Teaching Notes 4. Also explore the JSmols included in the antibody activity page and discuss the questions asked. Multiple chains: Q: This model has 4 different chains - the light chains are colored in shades of blue, while the heavy chains in shades of red, orange and pink. As you build the model, can you identify the primary, secondary, tertiary and quaternary structures of the Antibody molecule? A: As you assemble the long strips for each domain note that they represent the primary and secondary structure (the beta strands are marked). When you tape together the beta sheets in the beta barrel you are making the secondary structure. As each domain is assembled they represent tertiary structure. Assembling the complete antibody molecule (including all domains of the 4 protein chains) represents the quaternary structure. Disulfide bridges: Q: Each immunoglobulin domain has a disulfide bridge. When making the paper model notice how flexible the structure of each domain is, before and after attaching the disulfide link strip. What does this tell you about the function of the disulfide bridges? A: The disulfide bridges stabilize each immunoglobulin domain in the antibody model. Q: Disulfide bonds are formed as a result of an oxidation reaction. In which cellular compartment do you think disulfide linkages of the immunoglobulin are formed? (Hint: It is not in the cytoplasm.) A: The disulfide linkages are formed in the endoplasmic reticulum (ER). 5. Discuss the Fab and Fc regions of the antibody and how they are used in nature and research. Q: The anti-HIV antibody was found to have an extra long loop when compared to other antibodies. Can you suggest a reason why this long loop provides an advantage? A: HIV surface glycoproteins have sugars on the surface of the proteins. The extra-long loop can penetrate through the carbohydrates and bind to the protein portions to specifically recognize it. 6. Topics for further exploration: Q: What kinds of antibodies are commonly used in research and medicine? A: Antibodies used for research and medicine, usually need to be of a single specific type. For this purpose, monoclonal antibodies (mAb) are used in basic biomedical research, in diagnosis of disease, and in treatment of illnesses, such as infections and cancer. In some situations poly-specific antibodies may also be used. Q: How are monoclonal antibodies made? A: In order to produce monoclonal antibodies, an animal, usually a mouse is immunized and specific immune cells are obtained from its spleen. By fusing these cells with a cancer cell (such as cells from a myeloma) make them immortal, which means that they will grow and divide indefinitely. A tumor of the fused cells is called a hybridoma, and these cells Developed as part of the RCSB Collaborative Curriculum Development Program 2015 Teaching Notes secrete mAb. Thus the development of the immortal hybridoma requires the use of animals. Developed as part of the RCSB Collaborative Curriculum Development Program 2015