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Level: Advanced
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
a. Craft and Structure
i. RI.9-10.4
ii. RI.11-12.4
b. Integration of Knowledge and Ideas
i. RI.9-10.7
ii. RI.11-12.7
B. Next Generation Science Standards
a. Practices
i. 8. Obtaining, Evaluating and Communicating Information
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. PS2.B: Types of Interactions
C. Advanced Placement Biology - Essential Knowledge (EK), Learning Objectives (LO),
Science Practices (SP)
a. EK 4.A.1
i. LO 4.2, SP 1.3
ii. LO 4.3, SP 6.1, 6.4
Teaching Notes:
About Major Histocompatibility Complex (MHC):
1. Structure:
a. The MHC (Class I) is composed of two protein chains – Class I Histocompatibility
Antigen (HLA) and beta-2 microglobulin.
b. 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.
c. The other domain is a beta sandwich (Immunoglobulin domain) that interacts with
another immunoglobulin domain structure – the beta-2 microglobulin.
2. Function:
a. 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).
Developed as part of the RCSB Collaborative Curriculum Development Program 2015
Level: Advanced
Teaching Notes
MHC I, PDB ID 1hsa
An gen
b2
microglobulin
An gen
MHC II, PDB ID 1dlh
a chain
a chain
b chain
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. In PDB entry 1hla, how many polymer chains are there? What are they?
A1: There are 3 protein chains - HLA, beta-2 microglobulin and the antigen peptide
Q2. Where are the Cys residues located? Comment about how they are contributing to the stability
of the structure.
A2: 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. This bond stabilizes the antigen-binding cleft.
Q3. Based on your explorations of the binding neighborhood of the peptide from HIV-1 GP120
protein in PDB entry 1hhg, list 3 types of interactions that are stabilizing the peptide in the MHC I
molecule. List the residues involved in these interactions and show these interactions in 2-3 figures.
A3: There are several different interactions between the peptide and the MHC I molecule.
Examples of these interactions are listed below:
a. Hydrogen bonds – between amino terminus of peptide (residue 1) to Tyr171, Tyr
159, Glu63 and Tyr7 of MHC-I; Tyr 59 is hydrogen bonded to Tyr 171 of MHC-I
Developed as part of the RCSB Collaborative Curriculum Development Program 2015
Level: Advanced
Teaching Notes
All interacting residues around the N-terminus of the peptide are colored in yellow
and labeled.
b. Charge based interactions – Carboxy terminus of peptide (residue 9) to MHC-I Lys
146
The Lys residue interacting with the C-terminal peptide residue is colored yellow
and labeled.
c. Hydrophobic interactions –Peptide Leu2 and MHC Phe9 and Val67
Developed as part of the RCSB Collaborative Curriculum Development Program 2015
Level: Advanced
Teaching Notes
Residues participating in the hydrophobic interactions around Leu2 of the peptide
are shown in yellow and labeled.
Developed as part of the RCSB Collaborative Curriculum Development Program 2015