Protein Folding Diseases and Chaperones (CHM 4361 2022 Chapter 4.4)

A protein funnel is used to explain folding (and misfolding). Amyloid forms from the backbone coming together (So it could happen with ANY protein if there’s a lot of it unfolded). Alzheimer’s disease is associated with amyloid plaques in the brain after a protease cleaves and creates an unstable peptide, 40 or 42 residues long. X-ray crystallography gives repeated spacings like these two spacings for an amyloid fibril. The 40-residue fragment of Aβ folds differently from the 42-residue fragment (because the hydrophobic interaction is non-specific). Therefore, study of protein folding might save your life! For tau protein, different fibril structures associate with different diseases. Chaperones protect folding intermediates from aggregation. Chaperones may help some cancer cells survive.