Question

Systemic light chain amyloidosis (AL) is one of several protein misfolding diseases and is characterized by extracellular deposition of large quantities of antibodies in organs. A) While normal antibodies are comprised of a mix of sheets, helices, and random coils, circular dichroism spectroscopy of purified AL proteins shows a strong beta sheet signature. AL proteins are almost impossible to unfold, even in the presence of reducing agents, boiling, detergents, and chaotropic agents. How would you classify AL? B) If you could genetically engineer a human to treat AL, what type of protein might you want to overexpress in this patient? What kind of side effects may you see? (2 pts)

Answer 1

Ans a) AL stands for amyloid light chain and its occurrence is known for causing primary amyloidosis and it is caused when one’s antibody is not able to function properly due to its inability of it to fold properly. It tends to produce abnormal protein fibers from the light chains due to its misfolding. The improper folding occurs due to deposition of the insoluble fibrils with β-pleated sheet configuration. The deposit takes place either in systemic or localized manner. It is not possible to fold the AL and hence they can be classified based on the deposit of the protein fibers of amyloid

Ans b) In order to treat AL, there must be excess formation of light chain proteins which will be able to alter the antibodies and helps in correcting the problem of amyloidosis. Through genetic engineering of the light chain, it would help in treating the AL that are misfolded.