What the IRF6 Protein Looks Like
Take the reading one piece at a time. For each piece: read it once, underline the sentence that says what happens, then look up any word in the list. Tap a word to see its definition.
Piece 1 of 2
IRF6 is a protein 467 amino acids long that folds into two main working parts, called domains, joined by a floppy linker (real positions from UniProt O14896). The DNA-binding domain (DBD), residues 7 to 115, is a winged helix-turn-helix shape that physically clamps onto DNA so IRF6 can switch target genes on; it is encoded by exons 3 to 4. The protein-binding domain (SMIR / IAD) is C-terminal and links IRF6 to partner proteins so it can act as a team; it is encoded by exons 7 to 9. A disordered linker (residues 121 to 156) connects the two. R84 lives inside the DNA-binding domain.
Piece 2 of 2
Now place the Lesson 8 variants as positions on the map: R84C / R84H sit in the DNA-binding domain (residue 84) and abolish DNA binding (dominant-negative), causing severe PPS. L22P sits in the DNA-binding domain (residue 22) and abolishes DNA binding, causing VWS. S424L sits in the protein-binding domain and decreases transcriptional activity, causing PPS. A truncating change (e.g. R250X) cuts the chain so the domains past the cut are lost, causing haploinsufficiency and VWS. The big reported pattern: missense changes are enriched in the DNA-binding domain but not the protein-binding domain.
Reading the Research
- 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.
Now put it together: In one or two sentences, say what this whole reading is telling you about Mateo. Then go back to the lesson and fill in the guided notes.