Protein Structure Teacher Guide

Unit

Protein Structure

Subject

Biology

Grade Level

Activity Names

DNA Mutations

DNA to Proteins

Being Prepared

These activities are computer simulations, so having students as close to 1to1 with a computer is ideal. Plan significantly in advance of this activity to ensure you have access to computers (state testing requisitions, other teacher use, etc).

Laptops that require power cords should have power strips placed in such a way that walkways are kept clear.

Getting Started

The controls for the simulations are not always intuitive to new users. However, they always have very descriptive assistance provided in the text preceding the simulations. Encourage frustrated students to review the written instructions before attempting to interact with the model further.

There is no equipment required beyond a computer with sufficient power to run the simulations.

Suggested Timeline

Both activities fit best into a regular class period of 45 or 50 minutes when considering time for giving students instructions and technology setup and teardown. The two activities would not fit well together into a block period, and if they are to be used this way it is recommended to plan an intermediate activity to put between them that is more kinesthetic.

Thinking about the Discovery Questions

The DNA Mutations activity focuses on the discovery question: What are the different types of mutations? The Protein Structure activity focuses on the discovery question: What role does DNA play in protein structures? There is a popular idea in biology that has been termed "The Central Dogma". The Central Dogma states that information is stored in DNA by its sequence of nucleotides. It also states that same information is expressed by being translated to a sequence of amino acids comprising a protein dictated by the original sequence of nucleotides. This general belief regarding the behavior of biological information directs a wide variety of thinking across the field of biology.

Misconceptions

The primary misconception held by students when learning about the flow of information in a cell is that the process can be be overly simplified. While the basic flow of information can be grasped fairly quickly, the details of how information is moved become important in order to begin to explore the great many intricacies and exceptions in the process. At many points in the unit teachers do many things to help students grasp new material, but be wary of over simplifying the process. Push your students to wrestle with details they may rather overlook.

Learning Objectives

NGSS
- Performance Expectations
  - HS-LS1-1 Construct an explanation based on evidence for how the structure of DNA determines the structure of proteins which carry out the essential functions of life thorough systems of specialized cells.
  - HS-LS1-6 Construct and revise an explanation based on evidence for how carbon, hydrogen, and oxygen from sugar molecules may combine with other elements to form amino acids and/or other large carbon-based molecules.
  - HS-LS3-1 Ask questions to clarify relationships about the role of DNA and chromosomes in coding the instructions for characteristic traits passed from parents to offspring.
- Disciplinary Core Ideas
  - HS-LS1: From Molecules to Organisms: Structures and Processes
    - LS1.A: Structure and Function
      - Systems of specialized cells within organisms help them perform the essential functions of life. (HS-LS1-1)
      - All cells contain genetic information in the form of DNA molecules. Genes are regions in the DNA that contain the instructions that code for the formation of proteins, which carry out most of the work of cells. (HS-LS1-1) (secondary to HS-LS3-1)
    - LS1.C: Organization for Matter and Energy Flow in Organisms
      - The sugar molecules thus formed contain carbon, hydrogen, and oxygen: their hydrocarbon backbones are used to make amino acids and other carbon-based molecules that can be assembled into larger molecules (such as proteins or DNA), used for example to form new cells. (HS-LS1-6)
      - As matter and energy flow through different organizational levels of living systems, chemical elements are recombined in different ways to form different products. (HS-LS1-6),(HS-LS1-7)
  - HS-LS3: Heredity: Inheritance and Variation of Traits
    - LS3.A: Inheritance and Traits
      - Each chromosome consists of a single very long DNA molecule, and each gene on the chromosome is a particular segment of that DNA. The instructions for forming species’ characteristics are carried in DNA. All cells in an organism have the same genetic content, but the genes used (expressed) by the cell may be regulated in different ways. Not all DNA codes for a protein; some segments of DNA are involved in regulatory or structural functions, and some have no as-yet known function. (HS-LS3-1)
- Cross Cutting Concepts
  - Patterns
    - Students recognize that macroscopic patterns are related to the nature of microscopic and atomic-level structure. They identify patterns in rates of change and other numerical relationships that provide information about natural and human designed systems. They use patterns to identify cause and effect relationships, and use graphs and charts to identify patterns in data.
  - Cause and effect
    - Students classify relationships as causal or correlational, and recognize that correlation does not necessarily imply causation. They use cause and effect relationships to predict phenomena in natural or designed systems. They also understand that phenomena may have more than one cause, and some cause and effect relationships in systems can only be described using probability.
- Practices
  - Developing and using models
    - Develop and/or revise a model to show the relationships among variables, including those that are not observable but predict observable phenomena.
    - Develop and/or use a model to predict and/or describe phenomena.
    - Develop a model to describe unobservable mechanisms.
    - Develop and/or use a model to generate data to test ideas about phenomena in natural or designed systems, including those representing inputs and outputs, and those at unobservable scales.
  - Planning and carrying out investigations
    - Plan an investigation individually and collaboratively, and in the design: identify independent and dependent variables and controls, what tools are needed to do the gathering, how measurements will be recorded, and how many data are needed to support a claim.
    - Conduct an investigation and/or evaluate and/or revise the experimental design to produce data to serve as the basis for evidence that meet the goals of the investigation.
    - Collect data to produce data to serve as the basis for evidence to answer scientific questions or test design solutions under a range of conditions.
  - Analyzing and interpreting data
    - Analyze and interpret data to provide evidence for phenomena.
  - Constructing explanations and designing solutions
    - Construct an explanation using models or representations.
    - Construct a scientific explanation based on valid and reliable evidence obtained from sources (including the students’ own experiments) and the assumption that theories and laws that describe the natural world operate today as they did in the past and will continue to do so in the future.
    - Apply scientific ideas, principles, and/or evidence to construct, revise and/or use an explanation for real- world phenomena, examples, or events.
    - Apply scientific reasoning to show why the data or evidence is adequate for the explanation or conclusion.
  - Engaging in argument from evidence
    - Construct, use, and/or present an oral and written argument supported by empirical evidence and scientific reasoning to support or refute an explanation or a model for a phenomenon or a solution to a problem.
  - Obtaining, evaluating, and communicating information
    - Communicate scientific and/or technical information (e.g. about a proposed object, tool, process, system) in writing and/or through oral presentations.
NSES
- NSES Life Science - The Cell
  - Cells store and use information to guide their functions. The genetic information stored in DNA is used to direct the synthesis of the thousands of proteins that each cell requires.
  - Cells store and use information to guide their functions. The genetic information stored in DNA is used to direct the synthesis of the thousands of proteins that each cell requires.
- NSES Life Science - The Molecular Basis of Heredity
  - In all organisms, the instructions for specifying the characteristics of the organism are carried in DNA, a large polymer formed from subunits of four kinds (A, G, C, and T). The chemical and structural properties of DNA explain how the genetic information that underlies heredity is both encoded in genes (as a string of molecular "letters") and replicated (by a templating mechanism). Each DNA molecule in a cell forms a single chromosome.
  - Changes in DNA (mutations) occur spontaneously at low rates. Some of these changes make no difference to the organism, whereas others can change cells and organisms. Only mutations in germ cells can create the variation that changes an organism's offspring.
  - In all organisms, the instructions for specifying the characteristics of the organism are carried in DNA, a large polymer formed from subunits of four kinds (A, G, C, and T). The chemical and structural properties of DNA explain how the genetic information that underlies heredity is both encoded in genes (as a string of molecular "letters") and replicated (by a templating mechanism). Each DNA molecule in a cell forms a single chromosome.

Discussion: Setting the Stage

How is a molecule of DNA created out of individual atoms?

Bonds are broken and reformed between atoms of other molecules to produce a specific structure, the double helix. This would be a great time to use manipulatives or atomic models.
If you had to communicate English words (26 letter alphabet) using only our numbers (10 digits), how would you do it?

Use multiple digits to represent single letters.
What if you had to use our 26 letters to communicate numbers (10 digits) and every letter had to stand for something?

Make some of the letter duplicate, with multiple letters meaning the same number.

Discussion: Formative Questions

What part of the DNA can change along the strand?

The nitrogen bases can be different, with each base having any of the four possibilities [A, C, T, G].
What are the steps required to express the information contained in a DNA molecule?

DNA must be used to create messenger RNA, mRNA. mRNA then leaves the nucleus and is used to create an amino acid chain, a protein. The first process is called transcription and the second process is called translation.
What happens when a cell experiences a mutation?

A mutation is when any change occurs to the DNA sequence. Mutations can cause a cell to die, to become less able to survive, can have no effect at all, or in very rare cases can make the cell better able to survive.

Discussion: Wrapping Up

What kind of mutation has the greatest effect on a cell's DNA?

Choices can vary, but correct answers should contain the idea that any mutation that causes a frame-shift mutation has a catastrophic effect on the sequence in question.
There are three molecules closely related to the flow of information in a cell. What are those three molecules, and what role does each one fill in the cell?

DNA stores the cell's information, RNA moves the cell's information, and proteins express the cell's information.

Additional Background

Organisms big and small achieve the highly diverse structures and behaviors seen in nature through their highly varied protein structures. Humans use 21 amino acids to synthesize proteins, and that number fluctuates across the tree of life surprisingly little. Within those amino acids there are carbon rings, polar groups and nonpolar groups, acidic and basic groups, and even one with only an H for its side chain! The highly varied chemical properties of the amino acids themselves allows for a rich tapestry of proteins that can be built from the limitless combinations possible in any given amino acid chain.

In order to create useful chains of amino acids, cells store information for their proteins in the highly stable DNA molecules within their nucleus. DNA does not degrade over time the way proteins do, which allows them to pass the information for their proteins on to future generations. There is also an intermediate step in which DNA is used to create RNA before the protein is made. This allows a greater number of opportunities for regulation of the gene's expression, and the system is also most likely a relic from the first ancient cells that used RNA exclusively before the rise in use of DNA for storage and proteins for enzymatic activity.

Analysis

DNA Mutations

Do you think brachydactyly is an example of a genetic mutation? Explain your reasoning.

Yes and no... the condition is the result of a mutation. The condition itself is a result of an allele, either inherited or spontaneously arisen from a mutation.
Hydrophilic amino acids are attracted to water. Hydrophobic amino acids are not attracted to water, and tend to clump together. In the substitution model, was the synthesized amino acid hydrophobic?

Will vary. Use the color coded model to determine the result of each individual's mutation.
How can an insertion or deletion mutation make a protein much shorter than it should be?

Any mutation that creates a stop codon will cause the protein to be truncated at the spot of the mutation, possibly removing hundreds or thousands of amino acids from the downstream chain.
How did you create a silent mutation? Explain, giving the code for the triplet where you made your substitution, before and after the mutation.

Silent mutations are caused by exchanging a nitrogen base for a different base that creates a codon for the same amino acid as the original. This mutation is almost always in the third base of a triplet.

How did you make an insertion or deletion mutation that did not cause a frame-shift?

any insertion or deletion that contains a number of bases that is a multiple of three will not cause a frame-shift.
How can a mutation be neutral?

Any mutation that is silent is neutral, by definition. However, other mutations that don't cause any structural or chemical changes to the protein are also neutral. One example may be a mutation that changes the amino acid to one that is chemically similar and in a location that does not play a big role in the protein's function.
Which types of mutation, among those you created in this activity, are more likely to be lethal? Why?

Frame-shift mutations are much more likely to be lethal because they result in total destruction of all information downstream of the mutation.

What are the different types of mutations?

Insertion - addition of bases, deletion - removal of bases, substitution - change of one or more bases to different bases, duplication - insertion of bases with identical sequence to neighboring sequences, translocation - deletion of a sequence of DNA and an associated insertion of the same DNA sequence elsewhere in the genome, and inversion - changing a DNA sequence to its mirror opposite.
How can a mutation in a cell's DNA affect its growth?

A mutation can have any possible effect, positive or negative, depending on how it changes the efficiency of the protein being coded by that sequence.
What diseases would you want to search for a cure for if you were a cell biologist?

will vary.
Why do mutations that create a stop codon have a bigger effect on the protein than other mutations?

Creating a stop codon removes all downstream information, whereas other point mutations have a localized effect only on the codons they directly impact.

DNA to Proteins

There are millions of cells' worth of DNA in this tube. What do you think DNA looks like under a microscope?

will vary.
Describe the nucleotide pairings that you see.

will vary.
List two ways in which the RNA strand in the model above is different than DNA strand from which it was copied (the template strand). If six bases on the template strand of DNA are AGTAAC, what are the six bases on the complementary section of the RNA?

U is used instead of T, it is single stranded instead of double. RNA sequence is UCAUUG
What happens in translation? Compare the sequence and shape of both proteins that are formed.

will vary. Most notably is movement by 3 bases instead of one, and production of amino acid sequence instead of nucleic acid sequence.

Which one of the following is the place where genetic information is stored in the cell?

information is stored in the "strands of DNA"
How many nucleotides would you need to code for a protein with a sequence of 24 amino acid?

72. 24 x 3 bases per codon for each amino acid = 72
What is the connection between the DNA sequence of a gene and the amino acid sequence of the protein which is produced from that gene?

The DNA sequence dictates the RNA sequence, which dictates the amino acids used to build the protein. As a result, the DNA sequence controls the amino acid sequence produced.

What role does DNA play in protein structures?

DNA holds the information that dictates the resulting protein's structure.
Why do cell biologists work to discover the genomes of living things?

If we know the genome of a living thing, we can better understand the structure of that thing's proteins.
Would you want to be a cell biologist? Why or why not?

will vary.
If you change the code for Leucine, in the second codon, from UUG to AAA, what will be the end result?

Leucine will not be used in that spot on the amino acid chain. Instead Lycine will be used, which is hydrophilic instead of hydrophobic.

Further Investigation

The Central Dogma is only the beginning of how information flows in living systems. There are many exceptions, and students can investigate some of the less complex examples.

Prions are proteins that interact with other proteins to change their function. Prions cause some well known diseases, such as Mad Cow Disease. How is information transferred in prion function?

Diseased proteins transfer information to healthy proteins, which creates more diseased proteins. Protein &rarrow; Protein)
Some viruses transfer information in unconventional ways in order to reproduce. HIV uses a genome of RNA. What is the flow of information to create an HIV protein?

HIV creates DNA from RNA, which then creates more RNA, which is then used to create protein.