Download Biomolecular Structures and Modeling

Teaching Notes
Monitoring Student Learning
To assess if your students have learned about a biomolecular structures and modeling, you can
assign relevant Molecule of the Month features for them to read and then answer questions
about. Feel free to include additional questions to the basic question set to customize your
assessment.
Any Molecule of the Month article related to your/your students’ interests may be assigned. For
sample responses to the Questions asked about the Molecule of the Month articles - see below.
Example molecules include:
1. G-Proteins
2. TATA-Binding Protein
3. Glycolysis
4. Vitamin D
Developed as part of the RCSB Collaborative Curriculum Development Program 2015
Teaching Notes
1. Questions Based on the RCSB PDB Molecule of the Month
Go to the Molecule of the Month Article at the RCSB PPDB or PDB-101 websites (www.rcsb.org
or http://pdb101.rcsb.org/ respectively). Read the article and respond to the following
questions. *If there are 3 or more different proteins discussed in the article—e.g. as in the case of
the Glycolytic Enzymes—choose any one of the molecules to answer the starred (*) questions.
1. Which Molecule of the Month article did you read?
G Proteins
2. About the Featured Molecule(s)
a. Function: What is the main biological function discussed in the article?
G proteins are molecular switches, associated with various types of membrane
receptor molecules, on the inner surface of the cell membrane. Once the receptor
binds to its ligand, a message is received by the G proteins, which in turn initiate
the signal transduction pathway.
b. *Players: Name the key molecule(s) (proteins, nucleic acid, etc.) performing the
function(s) listed above? Are there any other molecules mentioned in the article
that interact with the molecule being studied – either facilitating or regulating the
discussed function? Name the molecule(s).
The alpha subunit (with bound GTP) of the G protein performs the main function.
Adenylyl cyclase is a molecule that supports this function. When the alpha subunit
of the G protein falls off, it moves along the membrane to find adenylyl cyclase and
activates it to produce cyclic AMP.
c. Big picture: Describe in 3-4 sentences how reading this article helps you
understand the function of a living organism or the world around you?
G proteins play a huge role in helping our body function efficiently. While they are
responsible for carrying important messages and facilitating metabolism, vision,
transmission of nerve signals, they are also a key target for many toxins and drugs.
Studying the structure of G proteins helps us understand its functions and develop
suitable drugs and inhibitors for specific instances of this class of molecules.
3. *Explore the structure-function relationship of the molecule(s) discussed in the article
a. Overview: Describe how the shape, size and interaction of relevant molecules
discussed in the article help in performing the function
Three different protein chains, called alpha, beta and gamma make up the GProtein. The alpha chain undergoes conformational changes upon binding to GTP
and GDP resulting in changes in the way they interact with the beta and gamma
chains. GTP is larger than GDP by one whole phosphate group. Exchange of GDP to
GTP leads to conformational changes, ultimately activating the G protein to
interact with the enzyme, Adenylate cyclase.
b. Details: Go to “Exploring the Structure” section in the article and analyze the
structures shown in detail.
i. Basic level: Examine the static images, and JSmol interactive views, where
available. If only static images are available, take a screen shot of the image,
include it in your answer and explain in 1-2 sentences the structural and
functional detail highlighted in it. In articles where the JSmol interactive
Developed as part of the RCSB Collaborative Curriculum Development Program 2015
Teaching Notes
views are available, take screenshots of at least two different views, and
include them in your answer. Explain in 1-2 sentences the structural and
functional details that these images highlight.
In the GDP bound form all three chains of the G-Protein non-covalently
interact with each other (figure labeled GDP (inactive), shown below.
Once the larger GTP replaces the GDP, a conformational change occurs,
allowing the protein to be in active form (shown below). When the G
Protein is in the active form (bottom left side), a short loop on the surface of
the protein created by the last phosphate group in the molecule allows it to
latch onto the surface, enabling it to later latch on to adenylyl cyclase when
found, thus beginning the cyclic AMP cascade.
ii. Advanced level: Click on any one of the 4-character accession code (PDB ID)
discussed in the “Exploring the Structure” section of the article. This should
lead you to the Structure Summary page of that PDB structure. Click on the
“3D View” tab and open a JSmol image that can be manipulated. Select from
the various visualization/customization options available. Take screenshots
of at least two different views highlighting structural details that are
important for its function, and include them in your answer. Include the
Developed as part of the RCSB Collaborative Curriculum Development Program 2015
Teaching Notes
PDB ID that you use, in your answer. Explain in 1-2 sentences the structural
and functional details that each of these images highlight.
The structure of active form of the alpha chain of G-Protein is seen in the
images below (from PDB entry 1gia). The image below shows two domains
with the GTP bound between them (highlighted in yellow). One of the
domains consists solely of alpha helices, whereas the other bottom part
includes both alpha helices and beta sheets.
In the image shown below, the same protein structure is shown in space-fill
mode, with all side-chains etc. shown. You can barely see the GTP here,
since it is concealed beneath the rest of the molecule.
Developed as part of the RCSB Collaborative Curriculum Development Program 2015
Teaching Notes
2. Questions Based on the RCSB PDB Molecule of the Month
Go to the Molecule of the Month Article at the RCSB PPDB or PDB-101 websites (www.rcsb.org
or http://pdb101.rcsb.org/ respectively). Read the article and respond to the following
questions. *If there are 3 or more different proteins discussed in the article—e.g. as in the case of
the Glycolytic Enzymes—choose any one of the molecules to answer the starred (*) questions.
4. Which Molecule of the Month article did you read?
TATA-Binding Protein
5. About the Featured Molecule(s)
a. Function: What is the main biological function discussed in the article?
TBP recognizes and binds to the TATA sequence on the promoter region.
b. *Players: Name the key molecule(s) (proteins, nucleic acid, etc.) performing the
function(s) listed above? Are there any other molecules mentioned in the article
that interact with the molecule being studied – either facilitating or regulating the
discussed function? Name the molecule(s).
In the images shown in the article the following proteins are shown:
-TBP: blue; protein, which will bind to DNA and help initialize transcription
-DNA: red; serves as the template, which is copied in transcription
-TFIID: green; a transcription factor, which is made up of TBP and other factors
-TFIIB: green; binds to the TBP-DNA complex; this new complex can recruit
additional transcriptional factors and promote transcription.
c. Big picture: Describe in 3-4 sentences how reading this article helps you
understand the function of a living organism or the world around you?
Transcription is the first step of gene expression, which is essential to protein
production, cell differentiation and therefore our growth. TBP binding to DNA is
the first step of the transcription process of eukaryotes. Understanding how TBP
binds can help us figure out regulation of the transcription process.
6. *Explore the structure-function relationship of the molecule(s) discussed in the article
a. Overview: Describe how the shape, size and interaction of relevant molecules
discussed in the article help in performing the function
TBP is a small protein that is able to grab the TATA sequence. TBP is composed of
two symmetrical halves that seem to sit on either side of the DNA strand and bend
it sharply.
b. Details: Go to “Exploring the Structure” section in the article and analyze the
structures shown in detail.
i. Basic level: Examine the static images, and JSmol interactive views, where
available. If only static images are available, take a screen shot of the image,
include it in your answer and explain in 1-2 sentences the structural and
functional detail highlighted in it. In articles where the JSmol interactive
views are available, take screenshots of at least two different views, and
include them in your answer. Explain in 1-2 sentences the structural and
functional details that these images highlight.
Developed as part of the RCSB Collaborative Curriculum Development Program 2015
Teaching Notes
ii. Advanced level: Click on any one of the 4-character accession code (PDB ID)
discussed in the “Exploring the Structure” section of the article. This should
lead you to the Structure Summary page of that PDB structure. Click on the
“3D View” tab and open a JSmol image that can be manipulated. Select from
the various visualization/customization options available. Take screenshots
of at least two different views highlighting structural details that are
important for its function, and include them in your answer. Include the
PDB ID that you use, in your answer. Explain in 1-2 sentences the structural
and functional details that each of these images highlight.
This representation shows TBP bound to DNA, in a space-fill view colored
by amino acid. Arginine and lysine are colored in dark blue while DNA is
colored in gray. These interactions are what bind TBP to DNA.
This second representation, in cartoon style and colored by secondary
structure, shows the symmetry of TBP and how the loops “grab” at the DNA
strand to bend it.
Developed as part of the RCSB Collaborative Curriculum Development Program 2015
Teaching Notes
3. Questions Based on the RCSB PDB Molecule of the Month
Go to the Molecule of the Month Article at the RCSB PPDB or PDB-101 websites (www.rcsb.org
or http://pdb101.rcsb.org/ respectively). Read the article and respond to the following
questions. *If there are 3 or more different proteins discussed in the article—e.g. as in the case of
the Glycolytic Enzymes—choose any one of the molecules to answer the starred (*) questions.
7. Which Molecule of the Month article did you read?
Glycolytic Enzymes
8. About the Featured Molecule(s)
a. Function: What is the main biological function discussed in the article?
These enzymes are the “workers” in the process of glycolysis. For example,
Hexokinase starts off glycolysis by transferring phosphate from ATP to glucose to
form glucose-6-phosphate.
b. *Players: Name the key molecule(s) (proteins, nucleic acid, etc.) performing the
function(s) listed above? Are there any other molecules mentioned in the article
that interact with the molecule being studied – either facilitating or regulating the
discussed function? Name the molecule(s).
Hexokinase: transfers phosphate ion from ATP to glucose. Thus ATP is needed by
hexokinase to start the glycolysis process
c. Big picture: Describe in 3-4 sentences how reading this article helps you
understand the function of a living organism or the world around you?
Glycolysis is a metabolic process that occurs in almost all cells. During glycolysis
glucose is partially broken down to provide energy. It is part of both aerobic and
anaerobic respiration. The enzymes discussed in this process are what drive the
glycolysis process.
9. *Explore the structure-function relationship of the molecule(s) discussed in the article
a. Overview: Describe how the shape, size and interaction of relevant molecules
discussed in the article help in performing the function
Hexokinase is shaped like a clamp so that when ATP and glucose are bound, the
hexokinase will close in on the two and protect them from water.
b. Details: Go to “Exploring the Structure” section in the article and analyze the
structures shown in detail.
i. Basic level: Examine the static images, and JSmol interactive views, where
available. If only static images are available, take a screen shot of the image,
include it in your answer and explain in 1-2 sentences the structural and
functional detail highlighted in it. In articles where the JSmol interactive
views are available, take screenshots of at least two different views, and
include them in your answer. Explain in 1-2 sentences the structural and
functional details that these images highlight.
ii. Advanced level: Click on any one of the 4-character accession code (PDB ID)
discussed in the “Exploring the Structure” section of the article. This should
lead you to the Structure Summary page of that PDB structure. Click on the
Developed as part of the RCSB Collaborative Curriculum Development Program 2015
Teaching Notes
“3D View” tab and open a JSmol image that can be manipulated. Select from
the various visualization/customization options available. Take screenshots
of at least two different views highlighting structural details that are
important for its function, and include them in your answer. Include the
PDB ID that you use, in your answer. Explain in 1-2 sentences the structural
and functional details that each of these images highlight.
Without glucose bound, hexokinase is shaped like a clamp. When glucose
binds, hexokinase closes around it and the groove is much smaller.
The first image shows Hexokinase with nothing bound to it. The second
image shows Hexokinase closing around ATP and glucose.
Developed as part of the RCSB Collaborative Curriculum Development Program 2015
Teaching Notes
4. Questions Based on the RCSB PDB Molecule of the Month
Go to the Molecule of the Month Article at the RCSB PPDB or PDB-101 websites (www.rcsb.org
or http://pdb101.rcsb.org/ respectively). Read the article and respond to the following
questions. *If there are 3 or more different proteins discussed in the article—e.g. as in the case of
the Glycolytic Enzymes—choose any one of the molecules to answer the starred (*) questions.
10. Which Molecule of the Month article did you read?
Vitamin D Receptor
11. About the Featured Molecule(s)
a. Function: What is the main biological function discussed in the article?
When vitamin D hormone binds to receptors, proteins involved in calcium
transport and utilization are produced.
b. *Players: Name the key molecule(s) (proteins, nucleic acid, etc.) performing the
function(s) listed above? Are there any other molecules mentioned in the article
that interact with the molecule being studied – either facilitating or regulating the
discussed function? Name the molecule(s).
-Vitamin D receptor acts as a communicator between vitamin D and nuclear
responses
-9-cis retinoic acid receptor (RXR) pairs up with vitamin D receptor to bind to
DNA.
-Enzymes make Vitamin D into hormone by adding hydroxyl groups to vitamin D
-Another special type of vitamin D binding protein takes individual molecules of
the hormone to sites of action.
c. Big picture: Describe in 3-4 sentences how reading this article helps you
understand the function of a living organism or the world around you?
Vitamin D regulates levels of calcium and phosphate in the body. It has especially
great impact on intestinal cells. A deficiency of vitamin D can lead to diseases such
as Rickets, so it is important to learn about how this receptor functions!
12. *Explore the structure-function relationship of the molecule(s) discussed in the article
a. Overview: Describe how the shape, size and interaction of relevant molecules
discussed in the article help in performing the function
There are two domains of vitamin D receptor. One binds to the vitamin D hormone,
while the other binds to DNA. Upon binding Vitamin D, the receptor forms a
heterodimer with RXR.
b. Details: Go to “Exploring the Structure” section in the article and analyze the
structures shown in detail.
i. Basic level: Examine the static images, and JSmol interactive views, where
available. If only static images are available, take a screen shot of the image,
include it in your answer and explain in 1-2 sentences the structural and
functional detail highlighted in it. In articles where the JSmol interactive
views are available, take screenshots of at least two different views, and
include them in your answer. Explain in 1-2 sentences the structural and
functional details that these images highlight.
Developed as part of the RCSB Collaborative Curriculum Development Program 2015
Teaching Notes
Native Receptor:
Mutant Receptor:
The backbone representation with
several atoms shown demonstrates
how the receptor surrounds the hormones molecules (spacefilled). One
option in the JSmol interactive shows the vitamin D receptor (purple
spacefill) in its native form while the other is a mutant form (Rickets
disease). The Native receptor representation shows how the hormone
receptor should actually work. The mutant receptor has a glutamine at
position 305 instead of histidine. This residue fits around the hormone
molecules differently and less efficiently (making a weaker hydrogen bond).
ii. Advanced level: Click on any one of the 4-character accession code (PDB ID)
discussed in the “Exploring the Structure” section of the article. This should
lead you to the Structure Summary page of that PDB structure. Click on the
“3D View” tab and open a JSmol image that can be manipulated. Select from
the various visualization/customization options available. Take screenshots
of at least two different views highlighting structural details that are
important for its function, and include them in your answer. Include the
PDB ID that you use, in your answer. Explain in 1-2 sentences the structural
and functional details that each of these images highlight.
Developed as part of the RCSB Collaborative Curriculum Development Program 2015