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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Chen, Yujie Ahmad, Basir Lapidus, Lisa J. |
| Description | Author Affiliation: Ahmad B ( Department of Physics and Astronomy, Michigan State University, East Lansing, MI 48824, USA.); |
| Abstract | We hypothesize that the first step of aggregation of disordered proteins, such as -synuclein, is controlled by the rate of backbone reconfiguration. When reconfiguration is fast, bimolecular association is not stable, but as reconfiguration slows, association is more stable and subsequent aggregation is faster. To investigate this hypothesis, we have measured the rate of intramolecular diffusion in -synuclein, a protein involved in Parkinson's disease, under solvent conditions that accelerate or decelerate aggregation. Using the method of tryptophan-cysteine (Trp-Cys) quenching, the rate of intramolecular contact is measured in four different loops along the chain length. This intrinsically disordered protein is highly diffusive at low temperature at neutral pH, when aggregation is slow, and compacts and diffuses more slowly at high temperature or low pH, when aggregation is rapid. Diffusion also slows with the disease mutation A30P. This work provides unique insights into the earliest steps of -synuclein aggregation pathway and should provide the basis for the development of drugs that can prevent aggregation at the initial stage. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 7 |
| Volume Number | 109 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2012-02-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Alpha-Synuclein Metabolism Circular Dichroism Diffusion Kinetics Molecular Dynamics Simulation Mutation Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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