Structure of beta-2-microglobulin amyloid fibrils in solutions with different pH

Ivan Sherstnev1, Olga Povarova1, Maksim Sulatsky1, Dmitry Polyakov2, Rodion Sakhabeev2, Anna Sulatskaya1

1 Institute of Cytology of the Russian Academy of Sciences, St. Petersburg, Russia
2 Institute of Experimental Medicine, St. Petersburg, Russia

Amyloid fibrils are fibrous protein aggregates that are associated with a number of presently incurable maladies, such as neurodegenerative diseases of Alzheimer's and Parkinson's, dialysis-related amyloidosis, malignant myeloma, etc. Dialysis-related amyloidosis is a serious complication of long-term dialysis therapy and is characterized by the deposition of amyloid fibrils, mainly composed of beta-2-microglobulins. In particular, the accumulation of beta-2-microglobulin amyloid plaques in the osteoarticular structures leads to the disruption of tissue architecture. These amyloid fibrils demonstrate remarkable stability, so the search for mechanisms of their structure disruption is a relevant task. This work was focused on the investigation of the pH effect on the beta-2-microglobulin amyloid fibrils structure.

The fibrils study was carrying out by electron microscopy, far-UV circular dichroism, intrinsic UV-fluorescence and fluorescence of amyloid-specific probe thioflavin T (ThT). It was found that amyloid fibrils are destroyed only in solutions with pH 12. At lower values of solutions pH, up to 1, amyloid fibrils are found in the sample. Thin and long fibrils are formed at extremely low pH (1 -3) and high pH (11) while at moderate pH (4 - 9) fibrils are thicker and aggregate with each other. So, the solution pH significantly influences on the beta-2-microglobulin amyloid fibrils structure: length and degree of their clusterization, number of binding sites to ThT and secondary structure.

This work was supported by grant 18-74-10100 from the Russian Scientific Foundation.