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oai:www.ideals.illinois.edu:2142/31996 2023-07-10 col_2142_5131 col_2142_14828 com_2142_5130 com_2142_14827 com_2142_14793 com_2142_8903

George, Julia M. Schulten, Klaus J. Martin, Gruebele H. Comellas Canal, Gemma 2012-06-27T21:23:42Z 2014-06-28T10:00:25Z 2012-05 2012-06-27T21:23:42Z 2012-05 In my thesis, I have focused on new methodology development combined with state-of-the-art solid-state nuclear magnetic resonance (NMR) experiments with scanning transmission electron microscopy (STEM) to obtain atomic level structural information of the alpha-synuclein (AS) fibrils and the mechanism of their formation; We first investigated the effect of protein deuteration and 1H decoupling optimization to maximize the resolution and sensitivity of biomolecular solid-state NMR; We then applied state-of-the-art solid-state NMR experiments to do a detailed structural characterization and conformational dynamics of AS fibrils using improved sample preparation and labeling schemes; These results show that the core of the fibrils extends for about 70 residues with a repeated secondary structure motif; Additionally, it demonstrates that the three mutation sites (A30P, E46K, A53T) are located in structured regions of the fibrils; Upon mutation, we have shown that the structure suffers major and minor perturbations by E46K and A53T, respectively; while the structure is unaltered by A30P; The fibril formation has also been investigated by capturing the transition from α-helical to β-sheet at the atomic level using solid-state NMR; Additionally, to investigate the AS fold, the mass-per-length (MPL) measurement of the fibrils has been obtained using STEM that together with solid-state NMR restraints have been used to propose possible models of how the fibrils arrange; Finally, initial results for solving 3D high-resolution structures of large proteins with new computational methods have been investigated. Rienstra, Chad M. Rienstra, Chad M. Item withdrawn by Mark Zulauf (zulauf@illinois.edu) on 2012-04-10T14:33:18Z Item was in collections: University of Illinois Theses & Dissertations (ID: 1) No. of bitstreams: 1 Comellas_Gemma.pdf: 38431208 bytes, checksum: b05713ea9a0a2d5f2661d8573d0bfc54 (MD5) Made available in DSpace on 2012-06-27T21:23:42Z (GMT). No. of bitstreams: 2 ComellasCanal_Gemma.pdf: 38431208 bytes, checksum: b05713ea9a0a2d5f2661d8573d0bfc54 (MD5) license.txt: 4064 bytes, checksum: 6e922a48608e0488ddb83d226329c3dd (MD5) Item marked as restricted to the 'UIUC Users [automated]' Group (id=2) by William Ingram (wingram2@illinois.edu) on 2012-06-27T21:24:47Z Item is restricted until 2014-06-27T21:24:27Z Item reinstated by Sarah Shreeves (sshreeve@illinois.edu) on 2014-06-28T10:00:25Z Item was in collections: Graduate Theses and Dissertations at Illinois (ID: 204) Dissertations - Biophysics and Computational Biology (ID: 689) No. of bitstreams: 2 ComellasCanal_Gemma.pdf: 38431208 bytes, checksum: b05713ea9a0a2d5f2661d8573d0bfc54 (MD5) license.txt: 4064 bytes, checksum: 6e922a48608e0488ddb83d226329c3dd (MD5) Item released from any restrictions by Sarah Shreeves (sshreeve@illinois.edu) on 2014-06-28T10:00:25Z http://hdl.handle.net/2142/31996 en Copyright 2012 Gemma Comellas Canal Nuclear magnetic resonance (NMR) magic-angle spinning (MAS) protein structure alpha-synuclein (AS) Structure, conformational dynamics and formation of large amyloids: the case of alpha-synuclein fibrils text School of Molecular & Cell Bio 1415 Biophysics & Computnl Biology 0319 University of Illinois at Urbana-Champaign Dissertation Ph.D. PHD:Biophys&Computnl Bio -UIUC 10KS0319PHD