{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/31996"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/31996","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Structure, conformational dynamics and formation of large amyloids: the case of alpha-synuclein fibrils","abstract":"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.","abstract_html":"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.","abstract_has_math":false,"creators":["Comellas Canal, Gemma"],"institution":"University of Illinois at Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"Biophysics & Computnl Biology","degree_department":null,"school":null,"contributors":["George, Julia M.","Schulten, Klaus J.","Martin, Gruebele H.","Rienstra, Chad M."],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2012,"date_issued":"2012-06-27T21:23:42Z","date_published":"2012-06-27T21:23:42Z","updated_at":"2026-07-22T22:25:30Z","subjects":["Nuclear magnetic resonance (NMR)","magic-angle spinning (MAS)","protein structure","alpha-synuclein (AS)"],"languages":["en"],"rights":["Copyright 2012 Gemma Comellas Canal"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/2142/31996","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["George, Julia M.","Schulten, Klaus J.","Martin, Gruebele H.","Rienstra, Chad M."]},{"key":"dc:creator","label":"Author","values":["Comellas Canal, Gemma"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2012-06-27T21:23:42Z","2014-06-28T10:00:25Z","2012-05"]},{"key":"dc:type","label":"Dc Type","values":["text"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Biophysics & Computnl Biology"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph.D."]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["University of Illinois at Urbana-Champaign"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Nuclear magnetic resonance (NMR)","magic-angle spinning (MAS)","protein structure","alpha-synuclein (AS)"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]},{"key":"dc:rights","label":"Dc Rights","values":["Copyright 2012 Gemma Comellas Canal"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/2142/31996"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["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.","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). 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