Seminars Archive

Conformation, Topology, Intermolecular arrangement and Polymorphism of Amyloid Fibrils: A Solid-State NMR view

Abstract
Amyloid fibrils or proteinaceous aggregates are not easily accessible to high-resolution structure determination, as they are neither crystalline nor soluble. In the recent decade, solid-state NMR spectroscopy has developed into a powerful tool to study even larger complex biological systems. In the past, we have investigated amyloid fibrils(1,2) and pre-fibrillar aggregates(3) of wild-type, and mutant alpha synuclein. Secondary structure, polymorphism, intersheet arrangement and topology could easily be identified. Furthermore, we will report initial results on fibrillar recombinant sheep PrP. 1. H. Heise, W. Hoyer, S. Becker, O.C. Andronesi, D. Riedel & M. Baldus. (2005). Molecular-level secondary structure, polymorphism, and dynamics of full-length ï¿¡-synuclein fibrils studied by solid-state NMR. Proc. Natl. Acad. Sci. USA 102, 15871-15876. 2. H. Heise, M.S. Celej, S. Becker, D. Riedel, A. Pelah, A. Kumar, T.M. Jovin & M. Baldus. (2008). Solid-State NMR Reveals Structural Differences between Fibrils of Wild-Type and Disease-Related A53T Mutant ï¿¡-Synuclein. J. Mol. Biol. 380, 444-450. 3. D.P. Karpinar, M.B.G. Balija, S. Kugler, F. Opazo, N. Rezaei-Ghaleh, N. Wender, H.-Y. Kim, G. Taschenberger, B.H. Falkenburger, H. Heise, A. Kumar, D. Riedel, L. Fichtner, A. Voigt, G.H. Braus, K. Giller, S. Becker, A. Herzig, M. Baldus, H. Jackle, S. Eimer, J.B. Schulz, C. Griesinger & M. Zweckstetter. (2009). Pre-fibrillar ï¿¡-synuclein variants with impaired ï¿¢-structure increase neurotoxicity in Parkinson\'s disease models. EMBO J 28, 3256-3268.