{"doi":"10.1101/2025.11.12.688092","title":"Proteome-wide identification of metamorphic protein candidates using mass spectrometry","abstract":"lysate. Methodological validation with the metamorphic protein Sa1V90T-whose α/β-plait and 3α states interchange between 30 °C and 5 °C-showed that a high-protease, short-digestion regime detects temperature-dependent exposure at four peptides, whereas the temperature-insensitive variant Sa1V90TV52D is largely unchanged. Applied to lysate, the workflow identifies >750 proteolytic sites across >250 abundant proteins (>10% of the identified proteome) whose local susceptibility shifts as temperature decreases from 35 °C to 5 °C, including five Sa1V90T peptides recapitulating purified-protein behavior. A site-level scoring model yields 338 destabilized peptides (177 proteins) and 426 stabilized peptides (138 proteins). Cold stabilization prominently marks translation machinery (>15 ribosomal proteins), while cooling also exposes regions in chaperones and cell-division factors. Sequence analysis links temperature sensitivity to charge-enriched composition, consistent with thermodynamic expectations. These data provide a proteome-wide view of cold-sensitive folding, implicate translation and cytokinetic systems in low-temperature remodeling, and illuminate a new strategy for identifying metamorphic proteins on an unprecedented scale.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":581489,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9308,"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":1267679,"name":"Yanping Qiu","orcid":"0000-0003-2948-2173","position":1,"is_corresponding":false},{"id":1335424,"name":"Kathleen Joyce Carillo","orcid":"0009-0006-1632-5709","position":2,"is_corresponding":false},{"id":378220,"name":"Andy LiWang","orcid":"0000-0003-4741-6946","position":3,"is_corresponding":false},{"id":393518,"name":"John Orban","orcid":"0000-0002-3895-1800","position":4,"is_corresponding":false},{"id":340064,"name":"Tsui‐Fen Chou","orcid":"0000-0003-2410-2186","position":5,"is_corresponding":false},{"id":731437,"name":"Baiyi Quan","orcid":"0000-0001-6313-4274","position":0,"is_corresponding":true}],"reference_count":47,"raw_metadata":null,"created_at":"2026-07-19T02:58:47.357782Z","pmid":"41292881","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":[]}