Rough draft.This research track is under review with Dr. Atit's lab. Content and sequence may still change.
Craniofacial Research Track
Session 12Reading the Evidence, DecemberLens: Human Body Systems
AlphaFold and UniProt: structure tells function
Discovery question
We say IRF6 binds DNA to switch genes on. What part of the actually does the binding, and how do scientists picture a shape no microscope can see?
A 's folded 3D shape determines what it can do. The is the business end of IRF6, and tools like let us see and trust that shape.
The plan
Prerequisite check
Before this page, you should know
- lines up two sequences position by position and reports , how much of the sequence matches.
- A is the same gene or in another species, descended from a shared ancestor.
If not, review
Today's new idea is only
A 's folded 3D shape determines what it can do. The is the business end of IRF6, and tools like let us see and trust that shape.
Learn first
What to learn
Goal: Open the structure for IRF6 (O14896), locate the , read the confidence (pLDDT) coloring, and use UniProt to confirm the domains, then connect structure to function.
Know by the end
- predicts a 's 3D structure and colors each part by confidence (pLDDT), dark blue is very high, orange is low.
- A domain is a distinct functional part of a ; IRF6 has a near its front (N-terminal) end.
- UniProt lists a 's domains and features with exact amino acid positions.
- The is what lets IRF6 act as a , so its shape explains its job.
The plan
Guided notes
1
See the shape
Model start: shows IRF6 as a folded chain with a compact region near one end and a less structured tail.
- Open the entry for O14896 and describe the overall shape in one sentence.
- Read the Model Confidence key and write what dark blue means versus orange.
2
Find the working part
Model start: UniProt lists a near the front of the ; on that region is mostly dark blue, meaning high confidence.
- On UniProt, open the Family and Domains section and write the name and amino acid range of the .
- Back on , look at the coloring over that domain. Is the model confident there?
3
Structure to function
- Write one sentence linking the 's shape to IRF6's job as a .
- Predict: if a changed the shape of the , what could go wrong for the cell?
Explore
Reading the Research
What to read
Read the overview section at the top of the page only. AlphaFold predicted structure of human IRF6 (O14896)
Why this source matters
This is the published evidence behind today's idea: A 's folded 3D shape determines what it can do. The is the business end of IRF6, and tools like let us see and trust that shape.
Words to unlock first
Reading moves
- Skim the title and abstract first to get the gist.
- Circle the one sentence that states the main claim.
- Box the evidence the authors give for that claim.
- Mark one sentence that confuses you, and move on.
Stop point
You do not need every detail on the page. Stay with the parts that connect to Mateo.
Your output
Write one claim-evidence sentence: what this source claims, and the one piece of evidence that backs it up.
Lab day
Use the real database
alphafold
- Open the entry at https://alphafold.ebi.ac.uk/entry/O14896 (O14896 is the UniProt accession for human IRF6).
- Look at the 3D viewer on the right. Use your mouse to rotate the structure (click and drag) and zoom (scroll) so you can see the whole fold.
- Find the Model Confidence key beside the viewer. Note the colors: dark blue is Very high (pLDDT over 90), light blue is Confident, yellow is Low, orange is Very low.
- Identify the compact, mostly dark-blue region near one end of the chain. This is the structured core that contains the .
- Open UniProt at https://www.uniprot.org/uniprotkb/O14896/entry in a second tab.
- In the left-side menu click Family & Domains (you can also click Features). Find the entry and write down its amino acid range.
- Go back to and check the coloring over that same range. Confirm whether the model is confident (blue) there, which it should be for a folded domain.
Turn in: An annotated note: a one-sentence description of IRF6's overall shape, the name and amino acid range of the (from UniProt), a note on its confidence color, and one sentence linking the domain's shape to IRF6's job as a .
Lab day
Using the database (what to capture)
AlphaFold
Open the tool Shows a predicted 3D shape of a , colored by how confident the prediction is.
When you use this: Use this when you have a variant and want to see WHERE in the folded it lands, so you can judge whether it sits in a part that matters.
What the screen looks like
Step by step
- 1Open .ebi.ac.uk and search the accession O14896 (human IRF6), or open the entry directly.
- 2Rotate the 3D model and find the near the front of the .
- 3Read the confidence color of that region from the legend (dark blue means trust the shape).
Capture these fields
- Confidence color (pLDDT band): Dark blue = very high, light blue = confident, yellow/orange = low
- Domain you are looking at: The DNA-binding domain near the front of the protein
- Amino-acid range: Roughly residues 13-113
How to read it: Dark-blue regions are predicted well and you can trust their shape; yellow/orange regions are flexible or uncertain, so do not over-read them. A change inside a well-folded, high-confidence domain is more likely to matter than one in a floppy, low-confidence loop.
Lost? How to read AlphaFold confidence UniProt
Open the tool The reference record for a : its length, its domains, and what each part does.
When you use this: Use this when you need to know which PART of the a variant hits, so you can predict whether it breaks a working region.
What the screen looks like
Step by step
- 1Open uniprot.org and search IRF6 human, then open entry O14896.
- 2Scroll to the Family and Domains section.
- 3Read the length and which domains exist (for example the ).
Capture these fields
- Accession (the protein's ID): O14896
- Length (amino acids): 467 aa
- Domains / regions: A DNA-binding domain and a protein-partner (SMIR) domain
How to read it: The domains tell you which part of the does which job. A variant that lands inside the is more likely to break IRF6's -factor function than one in a spacer region.
Lost? UniProt help: reading protein domains NCBI Gene
Open the tool The full reference record for a gene: its official symbol, ID, location, and what it does.
When you use this: Use this first, when you have a gene name and need its official ID and address. It is the home base every other database points back to.
What the screen looks like
Step by step
- 1Go to ncbi.nlm.nih.gov/gene and type the gene symbol IRF6 in the search box, then press Search.
- 2Open the top result whose organism is Homo sapiens (human).
- 3At the top of the record, read three things and write them down: the official symbol, the Gene ID number, and the location ( band).
Capture these fields
- Symbol (official gene name): IRF6
- Gene ID (the stable number): 3664
- Location (chromosome band): 1q32.2
- Summary (one line on its job): A transcription factor needed for the skin-surface cells that let the lip and palate fuse.
How to read it: The symbol and Gene ID let you find the exact same gene in every other database. The location should match the band you mapped (1q32). The summary tells you the gene's job in one sentence.
Lost? NCBI Gene help manual (how to use the Gene database)Learn first
Pick your level
Level 1, Guided
Use the sentence starters, a word bank from the vocabulary, a labeled diagram, and the exact source link.
Level 2, Collaborative
Complete a partly blank model or table and explain it.
Level 3, Independent
Make a claim from a new example or an unfamiliar entry in .
The plan
Work as a research team
Team roles
- Manager: keeps the group moving
- Recorder: writes the shared model or table
- Evidence checker: verifies each claim against the source
- Reporter: explains the group's reasoning
Process reflection
- What evidence changed your thinking today?
- What did your group disagree about, and how did you resolve it?
- What question is still unresolved?
Check yourself
Demonstration of learning
By the end of this session, submit ONE of: a labeled diagram with a 2-sentence explanation; a claim, evidence, reasoning paragraph; a completed data table from a real database; or a one-question exit ticket using today's vocabulary.
Recommended here: An annotated note: a one-sentence description of IRF6's overall shape, the name and amino acid range of the DNA-binding domain (from UniProt), a note on its AlphaFold confidence color, and one sentence linking the domain's shape to IRF6's job as a transcription factor.
Meets standard if your explanation correctly connects structure, timing, gene or protein function, or evidence source to Mateo's case: Open the AlphaFold structure for IRF6 (O14896), locate the DNA-binding domain, read the confidence (pLDDT) coloring, and use UniProt to confirm the domains, then connect structure to function.
How this is graded (rubric)
For: An annotated note: a one-sentence description of IRF6's overall shape, the name and amino acid range of the DNA-binding domain (from UniProt), a note on its AlphaFold confidence color, and one sentence linking the domain's shape to IRF6's job as a transcription factor.
| 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. |
How the model answer scores against this rubric
- CompleteProficient: Nothing is left blank: the model fills every part of "An annotated note: a one-sentence description of IRF6's overall shape, the name and amino acid range of the DNA-binding domain (from UniProt), a note on its AlphaFold confidence color, and one sentence linking the domain's shape to IRF6's job as a transcription factor.".
- 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.