{"doi":"10.1073/pnas.2215418120","title":"Reversible switching between two common protein folds in a designed system using only temperature","abstract":"Naturally occurring metamorphic proteins have the ability to interconvert from one folded state to another through either a limited set of mutations or by way of a change in the local environment. Here, we show in a designed system that it is possible to switch reversibly between two of the most common monomeric folds employing only temperature changes. We demonstrate that a latent 3α state can be unmasked from an α/β-plait topology with a single V90T amino acid substitution, populating both forms simultaneously. The equilibrium between these two states exhibits temperature dependence, such that the 3α state is predominant (>90%) at 5 °C, while the α/β-plait fold is the major species (>90%) at 30 °C. We describe the structure and dynamics of these topologies, how mutational changes affect the temperature dependence, and the energetics and kinetics of interconversion. Additionally, we demonstrate how ligand-binding function can be tightly regulated by large amplitude changes in protein structure over a relatively narrow temperature range that is relevant to biology. The 3α/αβ switch thus represents a potentially useful approach for designing proteins that alter their fold topologies in response to environmental triggers. It may also serve as a model for computational studies of temperature-dependent protein stability and fold switching.","journal":"Proceedings of the National Academy of Sciences","year":2023,"id":323559,"datarank":1.5594751095411479,"base_score":3.6109179126442243,"endowment":3.6109179126442243,"self_citation_contribution":0.5416376868966337,"citation_network_contribution":1.0178374226445142,"self_endowment_contribution":0.5416376868966337,"citer_contribution":1.0178374226445142,"corpus_percentile":null,"corpus_rank":null,"citation_count":36,"citer_count":31,"citers_with_citation_signal":27,"citers_with_endowment":27,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9492,"is_data_producer":true,"deposit_databanks":{"PDB":["00000132"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":393515,"name":"Yanan He","orcid":"0000-0002-0756-4306","position":1,"is_corresponding":false},{"id":1038817,"name":"Neşe Sari","orcid":null,"position":2,"is_corresponding":false},{"id":354374,"name":"Yihong Chen","orcid":"0000-0001-5176-4551","position":3,"is_corresponding":false},{"id":299793,"name":"D. Travis Gallagher","orcid":"0000-0003-1386-7255","position":4,"is_corresponding":false},{"id":993639,"name":"Philip N. Bryan","orcid":"0000-0001-7813-7523","position":5,"is_corresponding":false},{"id":393518,"name":"John Orban","orcid":"0000-0002-3895-1800","position":6,"is_corresponding":false},{"id":993637,"name":"Tsega L. Solomon","orcid":"0000-0003-1242-2297","position":0,"is_corresponding":true}],"reference_count":53,"raw_metadata":null,"created_at":"2026-07-19T01:07:52.377944Z","pmid":"36669114","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":[]}