How Does One Wrong Amino Acid Break the Protein?
Genetics domain · Lesson 12 of 20 · Medical Interventions (MI), with PBS overlap
Today's goal: Use an AlphaFold view of the IRF6 DNA-binding domain to connect structure to function, and predict how a single missense change disrupts either DNA binding directly or the fold itself.
What a finished product looks like
This is a model of the work you should turn in. Use it to check your own: match the structure and the level of detail, do not copy it. Your wording should be your own.
Prediction: This variant sits on the DNA-contacting surface and swaps a charged side chain for an uncharged one, so it removes a charge that helped grip the negatively charged DNA backbone. Losing that contact should weaken or abolish DNA binding, the same way R84C does when arginine becomes cysteine. I would call this variant likely damaging, because a residue on the load-bearing gripping surface of the conserved DNA-binding domain is exactly where a charge change breaks function. This reasoning is from structure-function, not a lookup; a ClinVar check would confirm it.
How this was built, step by step
The finished product above did not appear all at once. Here is the path from the question to the turned-in work, so you can follow the same steps.
- 1Start from today's question: How can changing one single amino acid in a 467-amino-acid stop the whole protein from doing its job?
- 2Work the Model and the Explore questions to reason it out before writing anything.
- 3Pull the specific evidence the product needs from the reading and any database you used.
- 4Write it up in the required format: A lab report lists a variant at a residue right on the DNA-contacting surface that swaps a charged for an uncharged one. In two or three sentences, predict the effect on DNA binding and state whether you would call this variant "likely damaging" or "likely tolerated," using reasoning, not a database lookup.
- 5Check it against the rubric, then submit.
| Criterion | Proficient | Developing | Beginning |
|---|---|---|---|
| Complete | Every required part of the artifact is present and filled in. | Most parts are present, but one is missing or left blank. | Several parts are missing. |
| Accurate | The science and data are correct and match the evidence. | Mostly correct, with a small factual slip. | Key science or data is wrong. |
| Scientific reasoning (CER) | States a claim, backs it with specific evidence, and explains the reasoning. | Has a claim and evidence, but the reasoning is thin or missing. | Gives an answer with no evidence or reasoning. |
| Professional communication | Clear, organized, and labeled the way a clinician or scientist would write it. | Readable but disorganized or missing labels. | Hard to follow. |
| Submitted | Turned in the right way (Schoology for routine work) and confirmed. | Turned in, but in the wrong place or unconfirmed. | Not turned in. |
- CompleteProficient: Nothing is left blank: the model fills every part of "A lab report lists a variant at a residue right on the DNA-contacting surface that swaps a charged side chain for an uncharged one. In two or three sentences, predict the effect on DNA binding and state whether you would call this variant "likely damaging" or "likely tolerated," using structure-function reasoning, not a database lookup.".
- AccurateProficient: Every number and claim matches the case evidence.
- Scientific reasoning (CER)Proficient: It names a claim, cites the specific evidence, and explains the reasoning, not just the answer.
- Professional communicationProficient: It is organized and labeled like a real chart note.
- SubmittedProficient: It would be turned in on Schoology and confirmed.
WebXam problem for today's skill
One exam-style question that uses exactly what you practiced today. Try it before you reveal the answer, then read why each choice is right or wrong.
Tap an answer to see the full explanation. Nothing is recorded or graded.