{"doi":"10.1021/acschembio.0c00543","title":"Unraveling the Mechanism of a LOV Domain Optogenetic Sensor: A Glutamine Lever Induces Unfolding of the Jα Helix","abstract":null,"journal":"ACS Chemical Biology","year":2020,"id":652994,"datarank":0.6141516843333151,"base_score":4.0943445622221,"endowment":4.0943445622221,"self_citation_contribution":0.6141516843333151,"citation_network_contribution":0.0,"self_endowment_contribution":0.6141516843333151,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":59,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":570385,"name":"Jinnette Tolentino Collado","orcid":null,"position":1,"is_corresponding":false},{"id":256391,"name":"Agnieszka A. 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Tonge","orcid":"0000-0003-1606-3471","position":20,"is_corresponding":false},{"id":409725,"name":"James N. Iuliano","orcid":"0000-0003-1213-3292","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Unraveling the Mechanism of a LOV Domain Optogenetic Sensor: A Glutamine Lever Induces Unfolding of the Jα Helix","abstract":"Light-activated protein domains provide a convenient, modular, and genetically encodable sensor for optogenetics and optobiology. Although these domains have now been deployed in numerous systems, the precise mechanism of photoactivation and the accompanying structural dynamics that modulate output domain activity remain to be fully elucidated. In the C-terminal light–oxygen–voltage (LOV) domain of plant phototropins (LOV2), blue light activation leads to formation of an adduct between a conserved Cys residue and the embedded FMN chromophore, rotation of a conserved Gln (Q513), and unfolding of a helix (Jα-helix) which is coupled to the output domain. In the present work, we focus on the allosteric pathways leading to Jα helix unfolding in Avena sativa LOV2 (AsLOV2) using an interdisciplinary approach involving molecular dynamics simulations extending to 7 μs, time-resolved infrared spectroscopy, solution NMR spectroscopy, and in-cell optogenetic experiments. In the dark state, the side chain of N414 is hydrogen bonded to the backbone N–H of Q513. The simulations predict a lever-like motion of Q513 after Cys adduct formation resulting in a loss of the interaction between the side chain of N414 and the backbone C═O of Q513, and formation of a transient hydrogen bond between the Q513 and N414 side chains. The central role of N414 in signal transduction was evaluated by site-directed mutagenesis supporting a direct link between Jα helix unfolding dynamics and the cellular function of the Zdk2-AsLOV2 optogenetic construct. Through this multifaceted approach, we show that Q513 and N414 are critical mediators of protein structural dynamics, linking the ultrafast (sub-ps) excitation of the FMN chromophore to the microsecond conformational changes that result in photoreceptor activation and biological function.","is_dataset_classified":null,"base_score":4.0943445622221,"endowment":4.0943445622221,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"32880430","pmcid":"PMC7572778","openalex_id":"https://openalex.org/W3083165499","authors":[],"funders":[{"funder_name":"Engineering and Physical Sciences Research Council","grant_id":"EP/N033647/1","title":"Structural Dynamics in LOV Domain Photosensor Proteins"},{"funder_name":"Directorate for Biological Sciences","grant_id":"MCB-1750637","title":null},{"funder_name":"Directorate for Biological Sciences","grant_id":"MCB-1817837","title":null},{"funder_name":"National Institute of Biomedical Imaging and Bioengineering","grant_id":"DP2EB024247","title":null},{"funder_name":"National Institute of General Medical Sciences","grant_id":"F32GM128304","title":null},{"funder_name":"National Institute of General Medical Sciences","grant_id":"R01GM106239","title":null},{"funder_name":"National Institute of General Medical Sciences","grant_id":"R25GM103962","title":null},{"funder_name":"National Institute of General Medical Sciences","grant_id":"T32GM092714","title":null},{"funder_name":"Bolyai Janos Research Fellow","grant_id":"OTKA NN113090","title":null},{"funder_name":"Engineering and Physical Sciences Research Council","grant_id":"EP/K000764/1","title":null},{"funder_name":"National Institutes of Health","grant_id":"1DP2EB024247-01","title":"Harnessing optogenetics to diagnose and therapeutically rewire cancer cell signaling"},{"funder_name":"National Institutes of Health","grant_id":"5R25GM103962-04","title":"Stony Brook University MERGE:  Maximizing Excellence in Research and Graduate Edu"},{"funder_name":"National Science Foundation","grant_id":"1750637","title":"CAREER:  Structural dynamics and mechanisms of photoreceptor signaling"},{"funder_name":"National Institutes of Health","grant_id":"5T32GM092714-07","title":"SBU Chemistry-Biology Interface Training Program"},{"funder_name":"National Institutes of Health","grant_id":"3R01GM106239-12S1","title":"Summer Undergraduate Research Support - Ms. Anastasiia Fisiuk"},{"funder_name":"National Institutes of Health","grant_id":"3F32GM128304-02S1","title":"Extracellular optogenetic control in the study of epithelial collective cell signaling"},{"funder_name":"National Science Foundation","grant_id":"1817837","title":"Photoreceptor Dynamics Over Ten Decades of Time"}],"total_grants":17,"fwci":6.0502,"citation_percentile":0.95937428,"influential_citations":0,"citation_trend":[{"year":2020,"count":2},{"year":2021,"count":8},{"year":2022,"count":6},{"year":2023,"count":12},{"year":2024,"count":11},{"year":2025,"count":11},{"year":2026,"count":9}],"oa_status":"green","license":"https://www.biorxiv.org/about/FAQ#license","oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/7572778","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/7572778","host_type":"repository"},{"url":"https://pubs.acs.org/doi/pdf/10.1021/acschembio.0c00543","host_type":"publisher"},{"url":"https://doi.org/10.1021/acschembio.0c00543","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/32880430","host_type":"repository"},{"url":"http://purl.org/net/epubs/work/48068446","host_type":"repository"},{"url":"https://doi.org/10.1101/2020.01.29.925040","host_type":""},{"url":"https://ueaeprints.uea.ac.uk/id/eprint/77740/1/Accepted_Manuscript.pdf","host_type":""},{"url":"https://dx.doi.org/10.1101/2020.01.29.925040","host_type":""},{"url":"https://dx.doi.org/10.1021/acschembio.0c00543","host_type":""},{"url":"http://dx.doi.org/10.1101/2020.01.29.925040","host_type":""},{"url":"https://doi.org/https://doi.org/10.1021/acschembio.0c00543","host_type":""}],"fields_of_study":["Light effects on plants","Photoreceptor and optogenetics research","Photosynthetic Processes and Mechanisms","0301 basic medicine","0303 health sciences","03 medical and health sciences"],"mesh_terms":["Protein Domains","Protein Conformation, alpha-Helical","Flavin Mononucleotide","Glutamine","Hydrogen Bonding","Light","Membrane Proteins","Mutation","Protein Binding","Mutagenesis, Site-Directed","Avena","Protein Multimerization","Molecular Dynamics Simulation","Phototropins","Protein Unfolding","Optogenetics"],"keywords":["Optogenetics","Allosteric regulation","Molecular switch","Biophysics","Helix (gastropod)","Phototropin","Chemistry","Molecular dynamics","Chromophore","Mutagenesis","Side chain","Protein structure","Stereochemistry","Cryptochrome","Biochemistry","Photochemistry","Biology","Mutation","Molecule","Enzyme","Protein Conformation, alpha-Helical","570","Phototropins","Avena","Light","Flavin Mononucleotide","Glutamine","Membrane Proteins","Hydrogen Bonding","Molecular Dynamics Simulation","540","Protein Domains","Mutagenesis, Site-Directed","Protein Multimerization","Protein Binding","Protein Unfolding"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"pdb"},{"name":"doi"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-10T17:45:42.871252Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}