Question

Explain what must happen in order for a folded globular protein to form an amyloid fiber.

Short answer

To form an amyloid fiber from a folded globular protein, it must have to be denatured. Denaturation can happen by cellular stress, and then fold themselves in an aggregation prone non-native structure, with their hydrophobic residues on their. By this proteins can aggregate with each other to form an amyloid fiber.

Step-by-step solution

Folded globular protein

Proteins have their distinct three dimensional structure, where the hydrophobic residues extend towards the interior of the protein and are shaded by the hydrophilic residues to avoid contact with the outside aqueous environment. This three dimensional structure comes from the folding of the protein molecule, and the native folding of protein is energetically stable.

Amyloid fiber

Amyloid fiber comes from the aggregation of misfolded proteins. Misfolded proteins represent an improper folding of the protein, giving rise to a non-native structure of the protein.

These misfolded proteins contain their hydrophobic residues on their surface, thus making them “sticky”. The sticky hydrophobic residues on the surface of one misfolded protein can attach with the sticky surface of another misfolded protein, leading to the aggregation of the protein.

Folded globular protein to amyloid fiber

Under cellular stress, such as heat, properly folded proteins can be denatured and tend to fold again. But sometimes,the proteins fold in their non-native structure which are prone to aggregation. Those misfolded proteins can aggregate to form amyloid fiber.