Effect of Metallothionein in b2-Microglobulin Fibrillogenesis
β2-microglobulin (β2m) is the precursor protein in dialysis-related amyloidosis. Fluorescence quenching of β2m with and without metallothionein (MT) by potassium iodide (KI) and acrylamide revealed that the binding interaction of the two proteins resulted in the exposure of tryptophan residues of β2m. Circular dichroism showed that β2m assumed a more ordered secondary structure upon binding with MT. The effect of MT on the fibrillogenesis of β2m was studied using the established Thioflavin-T assay. Fibril formation with and without MT both followed a pseudo-first order reaction. However, measurement of the initial rates of fibrillogenesis revealed that fibril formation was slower in the presence of MT. These results signify that the more ordered structure of β2m as a result of its binding with MT may prevent fibril formation. This is consistent with the fact that a partially unfolded structure of β2m is necessary for fibrillogenesis.
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