{"doi":"10.1021/acs.biochem.4c00217","title":"Deciphering the Molecular Dance: Exploring the Dynamic Interplay Between Mouse Insulin B9–23 Peptides and their Variants","abstract":"Type 1 diabetes results from the autoimmune destruction of pancreatic insulin-producing β-cells, primarily targeted by autoreactive T cells that recognize insulin B9-23 peptides as antigens. Using drift tube ion mobility spectrometry-mass spectrometry, transmission electron microscopy, and two-dimensional infrared spectroscopy, we characterized mouse insulin 1 B9-23 (Ins1 B9-23), insulin 2 B9-23 (Ins2 B9-23), along with two of their mutants, Ins2 B9-23 Y16A and Ins2 B9-23 C19S. Our findings indicate that Ins1 B9-23 and the Ins2 Y16A mutant exhibit rapid fibril formation, whereas Ins2 B9-23 and the Ins2 C19S mutant show slower fibrillization and a structural rearrangement from globular protofibrils to fibrillar aggregates. These differences in aggregation behaviors also manifest in interactions with (-)epigallocatechin gallate (EGCG), a canonical amyloid inhibitor. EGCG effectively disrupts the fibrils formed by Ins1 B9-23 and the Y16A mutant. However, it proves ineffective in preventing fibril formation of Ins2 B9-23 and the C19S mutant. These results establish a strong correlation between the aggregation behaviors of these peptides and their divergent effects on anti-islet autoimmunity.","journal":"Biochemistry","year":2024,"id":469021,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9498,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":998334,"name":"Kayla A. Hess","orcid":"0000-0002-6508-4423","position":1,"is_corresponding":false},{"id":1302450,"name":"Connor C. Long","orcid":"0000-0003-0945-2858","position":2,"is_corresponding":false},{"id":832409,"name":"Ethan J. Walker","orcid":"0000-0002-4376-7864","position":3,"is_corresponding":false},{"id":1302808,"name":"Joshua H. Jang","orcid":null,"position":4,"is_corresponding":false},{"id":1302809,"name":"Riellie J. DeSoto","orcid":null,"position":5,"is_corresponding":false},{"id":495063,"name":"Kristi Lazar Cantrell","orcid":null,"position":6,"is_corresponding":false},{"id":978864,"name":"Lauren E. Buchanan","orcid":"0000-0001-8486-0371","position":7,"is_corresponding":false},{"id":720820,"name":"D. Thanh","orcid":"0000-0002-1978-4365","position":8,"is_corresponding":false},{"id":720817,"name":"Aleksandra Antevska","orcid":"0000-0003-2669-2853","position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":null,"created_at":"2026-07-19T02:05:28.027781Z","pmid":"39222658","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":[]}