Calcium Binding to Beta
Beta-2-microglobulin (beta2m) is shed from MHCs and present in the serum which also contains calcium. We show that calcium binding to beta-2-microglobulin (beta2m) at physiological pH causes beta2m to undergo discernible conformational changes and undergo aggregation into amorphous aggregates that subsequently transform into amyloid aggregates, in a manner (and to a degree) which is entirely dependent on the concentrations of both calcium and beta2m. We show that calcium-bound beta-2m remains in a micro-aggregated soluble state under serum-like conditions of pH and calcium and beta2m concentration, with visible precipitates forming as either concentration is raised. This potentially explains both (i) how beta2m is trapped and destroyed through filtration-based processes in the body, and also (ii) how dialysis performed in patients of kidney disease probably pushes beta2m concentrations to levels that are high enough to cause aggregation and deposition of amorphous aggregates of the protein into bone joints, with subsequent transformation into amyloid aggregates that cause morbidity in the disease known as DRA (dialysis-related amyloidosis).