{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/129490"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/129490","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Single-molecule dynamics of GPCR signal transducers","abstract":"Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2027-05-01","abstract_html":"Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2027-05-01","abstract_has_math":false,"creators":["Deutsch, Jonathan C."],"institution":"University of Illinois Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"Biophysics & Quant Biology","degree_department":null,"school":null,"contributors":["Kobilka, Brian","Schroeder, Charles","Gruebele, Martin","Shukla, Diwakar"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2025,"date_issued":"2025-02-11","date_published":"2025-02-11","updated_at":"2026-07-22T22:25:05Z","subjects":["GPCRs","single molecule","dynamics."],"languages":["en","eng"],"rights":["Copyright 2025 Jonathan Deutsch"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/2142/129490","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Kobilka, Brian","Schroeder, Charles","Gruebele, Martin","Shukla, Diwakar"]},{"key":"dc:creator","label":"Author","values":["Deutsch, Jonathan C."]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2025-02-11","2025-05"]},{"key":"dc:type","label":"Dc Type","values":["text","Thesis"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Biophysics & Quant 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 Urbana-Champaign"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["GPCRs","single molecule","dynamics."]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en","eng"]},{"key":"dc:rights","label":"Dc Rights","values":["Copyright 2025 Jonathan Deutsch"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://hdl.handle.net/2142/129490"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2027-05-01","The student, Jonathan Deutsch, accepted the attached license on 2025-02-04 at 16:39.","The student, Jonathan Deutsch, submitted this Dissertation for approval on 2025-02-04 at 17:18.","This Dissertation was approved for publication on 2025-02-11 at 11:48.","DSpace SAF Submission Ingestion Package generated from Vireo submission #21631 on 2025-10-19 at 19:14:11","G protein-coupled receptors (GPCRs) transduce extracellular signals across the plasma membrane by coupling to heterotrimeric G proteins and arrestins. G proteins activate intracellular signaling cascades, while arrestins primarily attenuate G protein signaling and facilitate GPCR internalization and trafficking. Advances in structural biology have significantly improved our understanding of the molecular mechanisms underlying GPCR signal transduction by capturing distinct conformational states adopted by G proteins and arrestins along their activation pathways. However, a full understanding of GPCR-mediated signaling requires elucidating the dynamic interconversions between these metastable states and the conformational energy landscapes that govern them. In this work, I use single-molecule Förster resonance energy transfer (smFRET) imaging to investigate the dynamics of G proteins and arrestins during key stages of their activation by GPCRs. Chapter 2 focuses on the movements of the G protein α-helical domain, which undergoes displacement upon receptor coupling to facilitate nucleotide exchange and G protein activation. I show that these dynamics are affected by the agonist bound in the receptor's orthosteric pocket, suggesting a previously unrecognized role for the G protein in shaping ligand efficacy. Chapter 3 explores the autoinhibitory C-tail dynamics of a non-visual β-arrestin, identifying an intermediate conformational state that enables its recruitment to receptors with minimal or no C-terminal phosphorylation. Together, these single-molecule studies provide new insights into how both the initiation and termination of GPCR signaling are fine-tuned through the allosteric modulation of its transducer proteins’ structural dynamics."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Single-molecule dynamics of GPCR signal transducers"]}]}],"canonical_facts":{"dc:contributor":["Kobilka, Brian","Schroeder, Charles","Gruebele, Martin","Shukla, Diwakar"],"dc:creator":["Deutsch, Jonathan C."],"dc:date":["2025-02-11","2025-05"],"dc:description":["Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2027-05-01","The student, Jonathan Deutsch, accepted the attached license on 2025-02-04 at 16:39.","The student, Jonathan Deutsch, submitted this Dissertation for approval on 2025-02-04 at 17:18.","This Dissertation was approved for publication on 2025-02-11 at 11:48.","DSpace SAF Submission Ingestion Package generated from Vireo submission #21631 on 2025-10-19 at 19:14:11","G protein-coupled receptors (GPCRs) transduce extracellular signals across the plasma membrane by coupling to heterotrimeric G proteins and arrestins. G proteins activate intracellular signaling cascades, while arrestins primarily attenuate G protein signaling and facilitate GPCR internalization and trafficking. Advances in structural biology have significantly improved our understanding of the molecular mechanisms underlying GPCR signal transduction by capturing distinct conformational states adopted by G proteins and arrestins along their activation pathways. However, a full understanding of GPCR-mediated signaling requires elucidating the dynamic interconversions between these metastable states and the conformational energy landscapes that govern them. In this work, I use single-molecule Förster resonance energy transfer (smFRET) imaging to investigate the dynamics of G proteins and arrestins during key stages of their activation by GPCRs. Chapter 2 focuses on the movements of the G protein α-helical domain, which undergoes displacement upon receptor coupling to facilitate nucleotide exchange and G protein activation. I show that these dynamics are affected by the agonist bound in the receptor's orthosteric pocket, suggesting a previously unrecognized role for the G protein in shaping ligand efficacy. Chapter 3 explores the autoinhibitory C-tail dynamics of a non-visual β-arrestin, identifying an intermediate conformational state that enables its recruitment to receptors with minimal or no C-terminal phosphorylation. Together, these single-molecule studies provide new insights into how both the initiation and termination of GPCR signaling are fine-tuned through the allosteric modulation of its transducer proteins’ structural dynamics."],"dc:format":["application/pdf"],"dc:identifier":["https://hdl.handle.net/2142/129490"],"dc:language":["en","eng"],"dc:rights":["Copyright 2025 Jonathan Deutsch"],"dc:subject":["GPCRs","single molecule","dynamics."],"dc:title":["Single-molecule dynamics of GPCR signal transducers"],"dc:type":["text","Thesis"],"thesis:degree_discipline":["Biophysics & Quant Biology"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Ph.D."],"thesis:institution_name":["University of Illinois Urbana-Champaign"]},"updated_at":"2026-07-22T22:25:05Z"}