Structural Analysis of Aβ42 E22G Mutation Using AlphaFold

Background

Amyloid-beta (Aβ) peptides are central to Alzheimer’s disease pathology.
Aβ42, in particular, forms aggregates that are neurotoxic.
The E22G mutation (“Arctic mutation”) is known to increase aggregation tendency.

Objective

Compare the predicted 3D structures of normal Aβ42 and E22G mutant using AlphaFold (ColabFold).

Methods

• Software: ColabFold (AlphaFold2_mmseqs2)
• MSA mode: MMseqs2
• Sequences:
  • Normal: DAEFRHDSGYEVHHQKLVFFAEDVGSNKGAIIGLMVGGVVIA
  • E22G mutant: DAEFRHDSGYEVHHQKLVFFAGDVGSNKGAIIGLMVGGVVIA
• Outputs: .pdb files and structural visualizations

Results

Normal Aβ42

• Mostly flexible, small loops and transient helices
• Residue 22: glutamic acid (negatively charged)

E22G Mutant

• Increased flexibility at residue 22
• Exposed hydrophobic residues F19-F20
• Slight loss of helical content; more extended loops

Interpretation

• The E22G mutation increases local flexibility and exposes hydrophobic regions
• This structural change likely facilitates aggregation, consistent with disease mechanism

Files

• Notebooks: Interactive ColabFold runs
• PDB files: results/*/ranked_0.pdb
• Screenshots: Visualizations of predicted structures