Exploring a Protein Structure in the rcsb pdb: Antibodies Learning Goals

Level: Introductory

Teaching Notes

Exploring a Protein Structure in the RCSB PDB: Antibodies
Learning Goals:

1. 
   Visualize the structure of a given molecule using RCSB PDB resources.
   
2. 
   Explore the structure to understand its structure function relationships
   

Educational Standards

1. 
   Common Core
   
   1. 
      Craft and Structure
      
      1. 
         RI.9-10.4
         
      2. 
         RI.11-12.4
         
   2. 
      Integration of Knowledge and Ideas
      
      1. 
         RI.9-10.7
         
      2. 
         RI.11-12.7
         
2. 
   Next Generation Science Standards
   
   1. 
      Practices
      
      1. 
         8. Obtaining, Evaluating and Communicating Information
         
   2. 
      Crosscutting Concepts
      
      1. 
         3. Scale, proportion and quantity
         
      2. 
         4. Systems and system models
         
      3. 
         6. Structure and function
         
   3. 
      Disciplinary Core Ideas
      
      1. 
         LS1.A: Structure and Function
         
      2. 
         PS2.B: Types of Interactions
         
3. 
   Advanced Placement Biology - Essential Knowledge (EK), Learning Objectives (LO), Science Practices (SP)
   
   1. 
      EK 4.A.1
      
      1. 
         LO 4.2, SP 1.3
         
      2. 
         LO 4.3, SP 6.1, 6.4
         

Teaching Notes:
About Antibodies:

1. 
   Structure:
   
   1. 
      The antibody IgG is composed of 4 protein polymer chains – two light and two heavy chains.
      
   2. 
      Each of the light chains has two beta-sandwich domains (called immunoglobulin domains), while each heavy chain has four such domains.
      
   3. 
      The immunoglobulin domain has two beta sheets composed of 3-4 and 4-5 strands.
      
   4. 
      A single disulfide bond stabilizes each of the beta sandwich structures.
      
   5. 
      Additional disulfide bonds hold the 4 polymer chains together.
      
   6. 
      A number of saccharides (sugars) are covalently linked to the heavy chains in the IgG stem (part of antibody not binding to antigens). This makes IgG a glycoprotein and imparts structural stability to the molecule.
      

2. 
   Function:
   
   1. 
      The overall structure of the antibody is “Y-shaped” and has two antigen binding sites.
      
   2. 
      The immunoglobulin domains closest to the antigen binding regions vary from antibody to antibody resulting in specific antigen-antibody binding.
      
   3. 
      In the variable domain there are specific loops that directly touch the antigen and bind to it. The sequences of these loops are highly variable, imparting specificity to the antigen-antibody interactions.
      
   4. 
      Each antigen-binding site is composed of three hyper-variable loops from the heavy chain and three from the light chain.
      

Activity Suggestions:

1. 
   You may want your students to attempt this activity before they make the antibody paper model so that they are oriented to the overall shape and structure of the antibody IgG.
   
2. 
   Review the IgG structure with your students to make sure that they notice all the structural details described above.
   

Answers to Questions in Exercise:
Q1. What is the source of the antibody molecule in this structure?

A1. Mouse (Mus musculus)

Q2. Name the authors who solved the structure of this protein?

A2. Harris, L.J., Larson, S.B., Hasel, K.W., McPherson, A.

Q3. Describe the overall composition and organization of chains in the antibody structure. How many different protein chains do you see in this structure?

A3. There are 4 protein chains – 2 heavy and 2 light. The variable regions of pairs of heavy and light chains form the antigen binding site, while

Q4. What is the predominant secondary structural element that you see here?

A4. The predominant secondary structure seen here is beta sheets (that make up the immunoglobulin domains).

Q5. Describe what (if any) role these bonds play in holding the antibody structure together.

A5. There is one disulfide bond in each of the immunoglobulin domains stabilizing that fold. In addition disulfide bridges hold the 4 protein chains of the immunoglobulin together.

Developed as part of the RCSB Collaborative Curriculum Development Program 2015