3.) Protein Story Phase: Antibodies
Climbing the Mountain
Antibodies play a critical role in our adaptive immune system, identifying and neutralizing pathogens such as the novel coronavirus of the 2020 pandemic.
The resources below will introduce the basics of antibody structure and function. You will then choose a specific protein story related to antibodies that you want to model. You will read a scientific research article, find an antibody protein structure file, and design a 3D printed physical model of an antibody protein.
Note: If you skipped the Training Phase and need to review basic protein structure-function concepts, visit the Training Phase Protein Structure Resources.
Recommended Models for the Antibody Protein Story Phase
The MAPS program revolves around using physical models as teaching tools. So if at all possible, we encourage you to use the recommended models below for the antibody protein story phase.
All recommended models are available to borrow free of charge through the MSOE Lending Library, or are available for purchase through 3D Molecular Designs. Use the discount code below to receive a 10% MAPS discount on your 3D Molecular Designs purchases.
1. Introduction to Antibodies
In this section, we will explore the basic structure and functions of antibodies, including why we need them and how they help fight off pathogens as part of our adaptive immune system.
An Introduction to AntibodiesThe Adaptive Immune System is such an important part of modern medicine, that there have been multiple Nobel Prizes awarded in this area of research. Explore the Nobel Prize website link below to learn about some of these amazing discoveries, including three specific awards related directly to antibodies.
Nobel Prizes and the Immune System
- 1972 - Edelman and Porter - Anatomy of a Killer
- 1984 - Jerne, Kohler and Milstein - Creating Supply on Demand
- 1987 - Tonegawa - Assembly Instructions for Antibodies
The first Atomic-Resolution Structure of an Antibody was determined in 1973 and published by Pljak, Amzel, Avey, Chen, Phizackerley and Saul. Explore the PDF link below to see this early and groundbreaking article.
Pay special attention to the meticulously constructed models and figures shown throughout the paper. . . created well before easy-to-access molecular visualization programs like Jmol!
2. Antibody Structure
In this section we are going to explore the structure of an antibody. This key protein is very modular, being comprised of twelve near identical Immunoglobulin Folds.
The Modular Nature of AntibodiesYou have arrived at the first major modeling activity of the antibody module! In this modeling challenge, you will construct a physical, schematic model of an antibody using the 3DMD Antibody Student Pack or crafting materials of your choosing.
Modeling a Schematic Antibody
Your antibody model should highlighting the following features:
- Four Chains, two Heavy Chains and two Light Chains
- The N-terminal and C-terminal ends of each protein chain
- The Antigen Binding sites
- Each Chain is composed of immunoglobulin folds
- Each Chain is covalently linked to another Chain via disulfide bonds
When you are finished, take a photo of your model and share it with other MAPS Teams on the MAPS Discussion Boards.
A 3D Review of Antibody Structure
Now that you are familiar with basic antibody structure and have modeled a schematic antibody, use the link below to explore an antibody in full interactive 3D. This web page uses Jmol, the molecular visualization program you will later be using to create your own physical 3D printed antibody model.
3. Antibody Diversity
Antibodies play a key role in our adaptive immune system, binding to foreign objects such as the surface proteins on viruses or bacteria and marking them for destruction. The more pathogens our immune system is exposed to, the more diverse the collection of antibodies we will produce, each able to bind to a single specific pathogen fragment.
In this section of the module, we will explore how the antibody gene can produce such diversity.
Challenge 2: Calculating Antibody Diversity4. The Immunoglobulin Fold (IgG)
In this section, we will explore the modular immunoglobulin fold in more detail and create a physical model of a single IgG fold.
Challenge 3: Building Your Own IgG FoldBuilding an Immunoglobulin Fold
Using a 118 cm long mini-toober (from the 3DMD Antibody Student Modeling Pack), or any other flexible material (wire), create a physical model of an immunoglobulin fold. The model should accurately represent the path of the protein’s backbone in 3D space. The model can be based on the structure of Chain A described by 7kkj.pdb.
Before you begin to fold your model, mark on your mini-toober the position of the two cysteine amino acids that will form the covalent disulfide bond that stabilizes immunoglobulin fold.
Note that at this scale, you will not be able to represent the zig-zag shape of each strand of beta sheet. But your model should show the 4-stranded beta sheet and the 5-stranded beta sheet that makes up this fold.
Your final model should display the following features:
- The correct path of the protein’s backbone in 3D space.
- The two beta-sheets,… one with 4 strands and one with 5-strands.
- The disulfide bond connecting the two sheets
- The N-terminal end of your model
- CDRs 1, 2 and 3 (CDR is the abbreviation for Complementarity Determining Regions)
- EXTRA CREDIT: For the over-achievers among you, use Jmol to carefully examine the structure described by 7kkj.pdb … and find:
- An example of a salt bridge (an electrostatic interaction between an acid sidechain and a basic sidechain) that stabilizes this fold. Represent this salt bridge in some way on our model
- A pair of buried hydrophobic sidechains that stabilize the structure between the two beta sheets. Represent these hydrophobic sidechain in some way on your model
When you are finished, take a photo of your model and share it with other MAPS Teams on the MAPS Discussion Boards.
A Helpful Folding Guide
Folding an accurate model of an immunoglobulin fold is quite challenging, as the path of the protein backbone jumps back and forth between the top and bottom beta sheets. The link below can act as a helpful folding guide.
5. Defining Your Antibody Protein Story
Now that you are armed with an extensive understanding of what antibodies do and how their structure is important to their function, it is time to decide what specific antibody story you would like to explore.
The expandable content below will give you some suggested topics you may choose to focus on, a recommended antibody research paper to read, and link to a collection of antibody structure files you may choose to use when designing your 3D printed protein model.
The AeroNab StoryYour MAPS Team will want to have a clear idea of what your antibody story is before you start your model design. And one of the best ways to define your protein story is to write a scientific abstract.
Abstracts are, by definition, short. You might want to start with one sentence for each of the sections listed below, and then add additional sentences as needed.
- Introduction: What is the overall relevance of your protein of interest?
- Question: What is the particular story of your protein that your team will model?
- Findings: What answers to your question were you able to determine through your modeling project? Be specific as to what structural elements your team has modeled and how they are relevant to your story.
- Conclusion: How do your findings relate to the big picture? What important questions related to your protein story are still being actively researched?
Click here to see a sample abstract
Once you have defined the antibody protein story you want to tell, you will need to find a protein structure file that you can work with in Jmol to design your 3D printed antibody model.
Designing and building your own physical antibody model will give you great insight into specific structures that are important to the antibody protein story you have chosen to focus on. Even if you don't have your design 3D printed, studying the 3D design in specialized computer software is still helpful.
Below are a few additional links that may help you in your antibody structure search.
What Does it Mean to "Design" a Protein Model?
Tim Herman, PhD Explains How to Approach Your Model Design in Jmol
"Designing" a protein model means you explore a protein structure in Jmol, and then simplify the way the protein is visually displayed to make the key features of the protein that help communicate your molecular story more obvious.
This can mean hiding some atoms that are not important for your protein story, changing the display format of certain parts of your protein structure or changing colors to best highlight the most important parts of the protein structures. In the next section, you will learn the Jmol commands needed to accomplish this.
How to Approach Your Model Design
Tim Herman, PhD Explains How to Approach Your Model Design in Jmol
All 3D printed protein models made in the MAPS program are designed using the program Jmol. You start with a protein structure file (.PDB file), which contains the 3D locations of all of the atoms that make up the protein. Using the Jmol commands you will learn below, you can then edit the way the protein is displayed, hiding some atoms, changing display formats and customizing colors. When happy with your design, you can export your protein model from Jmol in file formats suitable for 3D printing.
We have created a detailed Jmol Training Guide that will cover everything you need to know to design and build your model. The Jmol Training Guide is broken down into four main sections, which we strongly recommend you explore in order until you are comfortable with Jmol and designing protein models for 3D printing.
- 1) Getting Started:
- Accessing Jmol
- Loading Structures
- Saving and Reloading - 2) Simplifying Your Protein:
- Exploring the Structure
- Focusing on the Backbone - 3) Adding the Details:
- Adding Sidechains
- Adding Ligands
- Adding Molecular Bonds - 4) 3D Printing Your Design:
- Adding Support Struts
- Checking Your Design
- Print it Yourself
- Pay Someone Else to Print it
Moving to the Next Phase
Once your team has finished the protein story phase, move on the Capstone Experience, where you will learn how to present your project using your 3D printed model and a variety of complimentary digital and print media.