1. Decreased Water Mobility Contributes To Increased α-Synuclein Aggregation
- Author
-
Amberley D. Stephens, Johanna Kölbel, Rani Moons, Chyi Wei Chung, Michael T. Ruggiero, Najet Mahmoudi, Talia A. Shmool, Thomas M. McCoy, Daniel Nietlispach, Alexander F. Routh, Frank Sobott, J. Axel Zeitler, Gabriele S. Kaminski Schierle, Stephens, Amberley D [0000-0002-7303-6392], Kölbel, Johanna [0000-0002-9820-1892], Moons, Rani [0000-0003-2961-9950], Chung, Chyi Wei [0000-0003-1780-3486], Ruggiero, Michael T [0000-0003-1848-2565], Mahmoudi, Najet [0000-0003-4936-6911], Shmool, Talia A [0000-0002-0415-3050], McCoy, Thomas M [0000-0002-4897-7924], Nietlispach, Daniel [0000-0003-4364-9291], Routh, Alexander F [0000-0002-3443-3053], Sobott, Frank [0000-0001-9029-1865], Zeitler, J Axel [0000-0002-4958-0582], Kaminski Schierle, Gabriele S [0000-0002-1843-2202], Apollo - University of Cambridge Repository, and Routh, Alex [0000-0002-3443-3053]
- Subjects
Amyloid ,Solvation Shell ,34 Chemical Sciences ,Forschungsartikel ,Water ,Parkinson Disease ,General Medicine ,General Chemistry ,Catalysis ,Hydration Shell ,Chemistry ,Hydrogen Bond ,Solvent ,3406 Physical Chemistry ,alpha-Synuclein ,Solvents ,Humans - Abstract
The solvation shell is essential for the folding and function of proteins, but how it contributes to protein misfolding and aggregation has still to be elucidated. We show that the mobility of solvation shell H2O molecules influences the aggregation rate of the amyloid protein alpha-synuclein (alpha Syn), a protein associated with Parkinson's disease. When the mobility of H2O within the solvation shell is reduced by the presence of NaCl, alpha Syn aggregation rate increases. Conversely, in the presence CsI the mobility of the solvation shell is increased and alpha Syn aggregation is reduced. Changing the solvent from H2O to D2O leads to increased aggregation rates, indicating a solvent driven effect. We show the increased aggregation rate is not directly due to a change in the structural conformations of alpha Syn, it is also influenced by a reduction in both the H2O mobility and alpha Syn mobility. We propose that reduced mobility of alpha Syn contributes to increased aggregation by promoting intermolecular interactions.
- Published
- 2023
- Full Text
- View/download PDF