Sulfate Inhibits Fibril Formation of β2-Microglobulin in vitro


James A. Villanueva1,2*, Christina P. Espiritu2, Rex Darell B. Vergel1,2 and Ma. Fritzie G. Reyes1

1Institute of Chemistry, University of the Philippines , Diliman, Quezon City
2Natural Sciences Research Institute, University of the Philippines Diliman,
Quezon City

corresponding author: This email address is being protected from spambots. You need JavaScript enabled to view it.



Beta-2-microglobulin (β2m) is a small MHC-I associated protein that undergoes aggregation and accumulates as amyloid deposits in human tissues as a consequence of long-term hemodialysis. Conditions that lead to fibril formation of β2m remain a largely unknown territory. Predisposing factors that will cause β2m to change from a soluble protein to an aggregate has been a topic of debate up to now. In this study, the effect of sulfate on β2m fibril formation was monitored through fluorescence spectroscopy employing the Thioflavin T assay. Sulfate was found to stabilize the native monomeric state of β2m at a 200-fold sulfate to protein ratio. Circular dichroism of β2m in the presence of sulfate indicated a spectrum characteristic of the natively folded protein rather than the amyloidogenic state. Electron microscopy analysis showed no needle-like fibrils formed in the presence of sulfate.



A growing number of proteins with the propensity to misfold and form amyloids fibril, under appropriate conditions, have been recognized to be associated with the pathology of some important human diseases. One such disease is dialysis related amyloidosis (DRA), a debilitating complication acquired . . . .




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