University of Illinois chemists, collaborating with peers at the University of Pennsylvania, Vanderbilt University and Queen Mary University of London, detailed their mapped structure of the protein alpha synuclein, in the journal Nature Structural and Molecular Biology.
In Parkinson’s, the protein alpha-synuclein forms long fibrils that disrupt brain activity. This is similar to the beta-amyloid fibrils that form in Alzheimer’s disease patients. However, while the beta-amyloid structure is known, the alpha-synuclein structure has eluded researchers as a result of its complexity, its insolubility and the difficulty of characterizing one protein within a fibril.
The Illinois group used a special type of molecular imaging called magic-angle spinning nuclear magnetic resonance to measure the placement of atoms in six different samples of alpha-synuclein. In each set of samples, they looked at different sets of atoms, then used advanced computational power to put them all together like pieces of a giant jigsaw puzzle.
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The group experimentally verified the structure with collaborators by producing the protein in the lab and checking it with various imaging methods to see if it matched the fibrils found in Parkinson’s patients. They also verified it biologically by testing it in cell cultures and seeing that it indeed behaved like the protein found in patients.
Marcus D Tuttle, Gemma Comellas, Andrew J Nieuwkoop, Dustin J Covell, Deborah A Berthold, Kathryn D Kloepper, Joseph M Courtney, Jae K Kim, Alexander M Barclay, Amy Kendall, William Wan, Gerald Stubbs, Charles D Schwieters, Virginia M Y Lee, Julia M George, Chad M Rienstra. Solid-state NMR structure of a pathogenic fibril of full-length human α-synuclein. Nature Structural & Molecular Biology, 2016; DOI: 10.1038/nsmb.3194