Question

Amyloidosis is caused by an abnormal deposition and accumulation of protein aggregates in tissues. How do proteins adopt and maintain a stable folded structure? What features of the protein amino acid sequence determine the stability of the folded structure? How does disruption of that structure lead to protein deposition diseases such as amyloidosis, Alzheimer's disease, and Parkinson's disease? Please respond to at least two classmates with additional questions and comments to further the discussion.

Please no handwritten or picture responses - only typed replies.

Answer 1

Each protein has a unique three dimensional structure and several non covalent interactions play a critical role in maintaining a stable conformation.

There are four levels of structural complexity for a protein molecule - Primary structure (linear chain of amino acids), secondary structure (alpha helix and beta sheets), tertiary structure (Polypeptide chain) and Quaternary structure (assembled subunits). Protein folding is a complex process that involves a complex transition from ensemble of unfolded conformations to a native structure which is capable of carrying out specific biological functions.

When protein denatures, it has a high conformational entropy. There are several reasons that can cause protein unfolding like mutations, alteration in environmental conditions. Once protein unfolds, there is an increase in the population of partially misfolded intermediates. The misfolded protein leads to the formation of amyloid aggregates. These amyloid aggregates are implicated in several neurdegenrative disorders like Alzheimer, Parkinson, Huntington and prion diseases.