{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/16525"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/16525","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Investigating the mechanisms of protein synthesis using multi-resolution structural data","abstract":"The ribosome is a complex, dynamic molecular machine responsible for protein synthesis in all cells according to the genetic information. Recent breakthroughs in ribosome crystallography culminated with the 2009 Nobel Prize in Chemistry. Concomitantly, advances in cryo-electron microscopy (cryo-EM) enabled the determination of images of the ribosome trapped in functional states at ever increasing resolution. In order to study different aspects of ribosome function at the atomic level, we developed the molecular dynamics flexible fitting (MDFF) method that combines X-ray and cryo-EM data, furnishing atomic models of the ribosome corresponding to functional intermediates. The MDFF-derived atomic models, combined with molecular dynamics simulations and other computational techniques, allowed us to address different research questions presented in this thesis. First, we found how ribosome-induced changes in the structure of elongation factor Tu leads to its GTPase activation, a crucial step in the decoding of genetic information. Next, we investigated structural and regulatory aspects of ribosomes in complex with a protein-conducting channel, which transports certain nascent proteins across or into membranes. Another area of investigation was the recognition of a regulatory nascent chain by the ribosome, as well as the mechanism by which it leads to translational stalling. Finally, we studied intermediate states of translocation of messenger and transfer RNAs through the ribosome, reconciling data from cryo-EM and single-molecule experiments.","abstract_html":"The ribosome is a complex, dynamic molecular machine responsible for protein synthesis in all cells according to the genetic information. Recent breakthroughs in ribosome crystallography culminated with the 2009 Nobel Prize in Chemistry. Concomitantly, advances in cryo-electron microscopy (cryo-EM) enabled the determination of images of the ribosome trapped in functional states at ever increasing resolution. In order to study different aspects of ribosome function at the atomic level, we developed the molecular dynamics flexible fitting (MDFF) method that combines X-ray and cryo-EM data, furnishing atomic models of the ribosome corresponding to functional intermediates. The MDFF-derived atomic models, combined with molecular dynamics simulations and other computational techniques, allowed us to address different research questions presented in this thesis. First, we found how ribosome-induced changes in the structure of elongation factor Tu leads to its GTPase activation, a crucial step in the decoding of genetic information. Next, we investigated structural and regulatory aspects of ribosomes in complex with a protein-conducting channel, which transports certain nascent proteins across or into membranes. Another area of investigation was the recognition of a regulatory nascent chain by the ribosome, as well as the mechanism by which it leads to translational stalling. Finally, we studied intermediate states of translocation of messenger and transfer RNAs through the ribosome, reconciling data from cryo-EM and single-molecule experiments.","abstract_has_math":false,"creators":["Trabuco, Leonardo G."],"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":["Schulten, Klaus J.","Baranger, Anne M.","Clegg, Robert M.","Ha, Taekjip"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2010,"date_issued":"2010-06-29T00:59:45Z","date_published":"2010-06-29T00:59:45Z","updated_at":"2026-07-22T22:25:09Z","subjects":["ribosome","molecular dynamics flexible fitting","Cryo-electron microscopy (cryo-EM)","Elongation factor Tu (EF-Tu)","SecY","TnaC","L1 stalk"],"languages":["en"],"rights":["Copyright 2010 Leonardo Giantini Trabuco"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/2142/16525","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Schulten, Klaus J.","Baranger, Anne M.","Clegg, Robert M.","Ha, Taekjip"]},{"key":"dc:creator","label":"Author","values":["Trabuco, Leonardo G."]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2010-06-29T00:59:45Z","2012-06-29T10:00:12Z","2010-5"]},{"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":["ribosome","molecular dynamics flexible fitting","Cryo-electron microscopy (cryo-EM)","Elongation factor Tu (EF-Tu)","SecY","TnaC","L1 stalk"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]},{"key":"dc:rights","label":"Dc Rights","values":["Copyright 2010 Leonardo Giantini Trabuco"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/2142/16525"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["The ribosome is a complex, dynamic molecular machine responsible for protein synthesis in all cells according to the genetic information. 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Next, we investigated structural and regulatory aspects of ribosomes in complex with a protein-conducting channel, which transports certain nascent proteins across or into membranes. Another area of investigation was the recognition of a regulatory nascent chain by the ribosome, as well as the mechanism by which it leads to translational stalling. Finally, we studied intermediate states of translocation of messenger and transfer RNAs through the ribosome, reconciling data from cryo-EM and single-molecule experiments.","Item withdrawn by Alexis Thompson (athmpsn1@illinois.edu) on 2010-03-26T21:00:56Z Item was in collections: University of Illinois Theses & Dissertations (ID: 1) No. of bitstreams: 1 Trabuco_Leonardo.pdf: 34092604 bytes, checksum: e0a52be6353c848e7b088c072441eb8c (MD5)","Made available in DSpace on 2010-06-29T00:59:45Z (GMT). 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Next, we investigated structural and regulatory aspects of ribosomes in complex with a protein-conducting channel, which transports certain nascent proteins across or into membranes. Another area of investigation was the recognition of a regulatory nascent chain by the ribosome, as well as the mechanism by which it leads to translational stalling. Finally, we studied intermediate states of translocation of messenger and transfer RNAs through the ribosome, reconciling data from cryo-EM and single-molecule experiments.","Item withdrawn by Alexis Thompson (athmpsn1@illinois.edu) on 2010-03-26T21:00:56Z Item was in collections: University of Illinois Theses & Dissertations (ID: 1) No. of bitstreams: 1 Trabuco_Leonardo.pdf: 34092604 bytes, checksum: e0a52be6353c848e7b088c072441eb8c (MD5)","Made available in DSpace on 2010-06-29T00:59:45Z (GMT). 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