Level: Introductory

Teaching Notes

Exploring a Protein Structure in the RCSB PDB: Major Histocompatibility Complex

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

A.  Common Core

  1. Craft and Structure
  2. RI.9-10.4
  3. RI.11-12.4
  4. Integration of Knowledge and Ideas
  5. RI.9-10.7
  6. RI.11-12.7

B.  Next Generation Science Standards

  1. Practices
  2. 8. Obtaining, Evaluating and Communicating Information
  3. Crosscutting Concepts
  4. 3. Scale, proportion and quantity
  5. 4. Systems and system models
  6. 6. Structure and function
  7. Disciplinary Core Ideas
  8. LS1.A: Structure and Function
  9. PS2.B: Types of Interactions

C.  Advanced Placement Biology - Essential Knowledge (EK), Learning Objectives (LO), Science Practices (SP)

  1. EK 4.A.1
  2. LO 4.2, SP 1.3
  3. LO 4.3, SP 6.1, 6.4

Teaching Notes:

About Major Histocompatibility Complex (MHC):

1.  Structure:

  1. The MHC (Class I) is composed of two protein chains – Class I Histocompatibility Antigen (HLA) and beta-2 microglobulin.
  2. The HLA chain has two domains – one that binds the peptide antigen in a cleft with a beta sheet at its base and in between two helices.
  3. The other domain is a beta sandwich (Immunoglobulin domain) that interacts with another immunoglobulin domain structure – the beta-2 microglobulin.

2.  Function:

  1. The antigenic peptide binds to the cleft in the HLA chain. (Note: in the Class II MHC molecule the antigen binding cleft is composed of two different chains).

  1. The appropriate T-Cell Receptor binds to both the MHC molecule and bound antigen in a specific way to trigger signals in the T-cell.

Answers to Questions in Exercise:

Q1. What is the source (organism) of the Class I Histocompatibility Antigen molecule in this structure?

A1. Human (Homo sapiens)

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

A2. Madden, D.R., Gorga, J.C., Strominger, J.L., Wiley, D.C.

Q3. How many different protein chains do you see in this structure?

A3. 3 chains – HLA, beta-2 microglobulin and the antigen peptide.

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

A4. The MHC (Class I) structure has regions with beta sheets and sandwiches as well as helices (at the edge of the antigen binding cleft).

Q5. Describe what (if any) role the S-S bonds play in holding the MHC structure together. A5. A single S-S bond stabilizes each of the immunoglobulin domains. In addition, there is an S-S bond between one of the helices surrounding the antigen binding cleft and the beta sheet forming the base of the cleft.

Developed as part of the RCSB Collaborative Curriculum Development Program 2015