{"doi":"10.1021/acs.biochem.3c00526","title":"β-Hairpin Alignment Alters Oligomer Formation in Aβ-Derived Peptides","abstract":"High Resolution Image Download MS PowerPoint Slide Amyloid-β (Aβ) forms heterogeneous oligomers, which are implicated in the pathogenesis of Alzheimer’s disease (AD). Many Aβ oligomers consist of β-hairpin building blocks─Aβ peptides in β-hairpin conformations. β-Hairpins of Aβ can adopt a variety of alignments, but the role that β-hairpin alignment plays in the formation and heterogeneity of Aβ oligomers is poorly understood. To explore the effect of β-hairpin alignment on the oligomerization of Aβ peptides, we designed and studied two model peptides with two different β-hairpin alignments. Peptides Aβm 17–36 and Aβm 17–35 mimic two different β-hairpins that Aβ can form, the Aβ 17–36 and Aβ 17–35 β-hairpins, respectively. These hairpins are similar in composition but differ in hairpin alignment, altering the facial arrangements of the side chains of the residues that they contain. X-ray crystallography and SDS-PAGE demonstrate that the difference in facial arrangement between these peptides leads to distinct oligomer formation. In the crystal state, Aβm 17–36 forms triangular trimers that further assemble to form hexamers, while Aβm 17–35 forms tetrameric β-barrels. In SDS-PAGE, Aβm 17–36 assembles to form a ladder of oligomers, while Aβm 17–35 either assembles to form a dimer or does not assemble at all. The differences in the behavior of Aβm 17–36 and Aβm 17–35 suggest β-hairpin alignment as a source of the observed heterogeneity of Aβ oligomers.","journal":"Biochemistry","year":2024,"id":464510,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9546,"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":678465,"name":"Adam G. Kreutzer","orcid":"0000-0002-9724-6298","position":1,"is_corresponding":false},{"id":378138,"name":"Nicholas L. Truex","orcid":"0000-0002-7369-685X","position":2,"is_corresponding":false},{"id":168285,"name":"James S. Nowick","orcid":"0000-0002-2273-1029","position":3,"is_corresponding":false},{"id":1106531,"name":"Sarah M. Ruttenberg","orcid":"0000-0003-4739-0619","position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":null,"created_at":"2026-07-19T02:04:42.082401Z","pmid":"38163326","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":[]}