{"doi":"10.1073/pnas.2426324122","title":"State-dependent motion of a genetically encoded fluorescent biosensor","abstract":"Genetically encoded biosensors can measure biochemical properties such as small-molecule concentrations with single-cell resolution, even in vivo. Despite their utility, these sensors are \"black boxes\": Very little is known about the structures of their low- and high-fluorescence states or what features are required to transition between them. We used LiLac, a lactate biosensor with a quantitative fluorescence-lifetime readout, as a model system to address these questions. X-ray crystal structures and engineered high-affinity metal bridges demonstrate that LiLac exhibits a large interdomain twist motion that pulls the fluorescent protein away from a \"sealed,\" high-lifetime state in the absence of lactate to a \"cracked,\" low-lifetime state in its presence. Understanding the structures and dynamics of LiLac will help to think about and engineer other fluorescent biosensors.","journal":"Proceedings of the National Academy of Sciences","year":2025,"id":517996,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9568,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":957633,"name":"Samantha M. Horwitz","orcid":"0000-0002-5407-7674","position":1,"is_corresponding":false},{"id":289943,"name":"Daniel J. Brooks","orcid":"0000-0001-7408-9851","position":2,"is_corresponding":false},{"id":798490,"name":"Erica Kim","orcid":null,"position":3,"is_corresponding":false},{"id":957634,"name":"Joseph A. Ambarian","orcid":"0000-0002-1465-8423","position":4,"is_corresponding":false},{"id":1385429,"name":"Lidia M Waidmann","orcid":null,"position":5,"is_corresponding":false},{"id":777107,"name":"Katherine M. Davis","orcid":"0000-0002-0258-8907","position":6,"is_corresponding":false},{"id":245308,"name":"Gary Yellen","orcid":"0000-0003-4228-7866","position":7,"is_corresponding":false},{"id":480400,"name":"Paul C. Rosen","orcid":"0000-0001-7414-454X","position":0,"is_corresponding":true}],"reference_count":57,"raw_metadata":null,"created_at":"2026-07-19T02:49:04.756302Z","pmid":"40048274","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":[]}