The Effects of Acetylation on Beta‐2‐Microglobulin on Amyloid Formation

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Beta‐2‐Microglobulin (B2m) is a small 99 residue globular protein that is a part of the type I major histocompatibility complex found on all nucleated cells. It is shed from the surface of cells into the bloodstream as cells undergo apoptosis then is degraded and excreted from the body in people with normal functioning kidneys. However, B2m is not effectively removed from the blood by hemodialysis causing systemic problems for patients in end‐stage kidney disease (ESKD). B2m serum levels in patients with ESKD are up to 60 times greater than healthy individuals. Dialysis related amyloidosis (DRA), is a disease that is often experienced by those with ESKD. DRA results from the accumulation of misfolded B2m and is characterized by carpal tunnel like symptoms coupled with chronic joint inflammation. DRA is a result of the deposition of misfolded B2m in the musculoskeletal system due to B2m amyloid plaque formation. However, the increased concentration of B2m alone is not sufficient to trigger the pathogenic amyloidosis at physiological pH. Thus, a secondary factor must be acting as the trigger of misfolding. This study is investigating the effect of acetylation as a non‐natural post translational modification on B2m. Acetylation is a practicable suspect as aspirin consumption is known to acetylate a variety of proteins non‐specifically. The acetylation of lysines would alter the overall charge and possibly disrupt ability of B2m to maintain its native state conformation thus increasing the aggregation propensity of B2m. We are primarily testing the susceptibility of B2m to acetylation via protocol established for acetylation in bovine carboxy anhydrase. Additionally, growth of the amyloid fibrils of the acetylated B2m will be monitored with thioflavin‐T fluorescence to assess the effects of lysine acetylation on B2m amyloid formation.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.