B2M Folding Project
The Richardson Lab focuses on understanding the mechanistic basis of protein folding and the misfolding process with respect to the disease dialysis-related amyloidosis (DRA). The model protein to be investigated is b-2-microglobulin (b2m), the fibrous component of amyloid deposits in DRA. The associated downstream effects of this disease on long-term cardiac, renal, and cartilaginous joint health make it an ideal candidate for study, not only for the advancement of fundamental scientific knowledge, but also for the broader application to public health. b2m is a 99-residue protein with a classical immunoglobulin fold and is necessary for the cell surface expression of the major histocompatibility complex. DRA is characterized by accumulation of b2m deposits leading to severe joint pain and immobility. Currently the only treatment for DRA includes filtration of blood during hemodialysis. While filtration may remove large aggregates it does not stop the misfolded “seed” particles from reentering circulation and propagation of the disease. Projects include expression, purification and characterization of wild-type protein and site directed mutants.