{"doi":"10.1016/j.csbj.2023.12.023","title":"Sequence-based identification of amyloidogenic β-hairpins reveals a prostatic acid phosphatase fragment promoting semen amyloid formation","abstract":"β-Structure-rich amyloid fibrils are hallmarks of several diseases, including Alzheimer's (AD), Parkinson's (PD), and type 2 diabetes (T2D). While amyloid fibrils typically consist of parallel β-sheets, the anti-parallel β-hairpin is a structural motif accessible to amyloidogenic proteins in their monomeric and oligomeric states. Here, to investigate implications of β-hairpins in amyloid formation, potential β-hairpin-forming amyloidogenic segments in the human proteome were predicted based on sequence similarity with β-hairpins previously observed in Aβ, α-synuclein, and islet amyloid polypeptide, amyloidogenic proteins associated with AD, PD, and T2D, respectively. These three β-hairpins, established upon binding to the engineered binding protein β-wrapin AS10, are characterized by proximity of two sequence segments rich in hydrophobic and aromatic amino acids, with high β-aggregation scores according to the TANGO algorithm. Using these criteria, 2505 potential β-hairpin-forming amyloidogenic segments in 2098 human proteins were identified. Characterization of a test set of eight protein segments showed that seven assembled into Thioflavin T-positive aggregates and four formed β-hairpins in complex with AS10 according to NMR. One of those is a segment of prostatic acid phosphatase (PAP) comprising amino acids 185-208. PAP is naturally cleaved into fragments, including PAP(248-286) which forms functional amyloid in semen. We find that PAP(185-208) strongly decreases the protein concentrations required for fibril formation of PAP(248-286) and of another semen amyloid peptide, SEM1(86-107), indicating that it promotes nucleation of semen amyloids. In conclusion, β-hairpin-forming amyloidogenic protein segments could be identified in the human proteome with potential roles in functional or disease-related amyloid formation.","journal":"Computational and Structural Biotechnology Journal","year":2023,"id":381352,"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":0.9524,"is_data_producer":false,"deposit_databanks":null,"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":1146900,"name":"Emil Dandanell Agerschou","orcid":"0009-0000-5676-6126","position":1,"is_corresponding":false},{"id":270827,"name":"Asuka A. Orr","orcid":"0000-0003-4628-526X","position":2,"is_corresponding":false},{"id":1146901,"name":"Tatsiana Kupreichyk","orcid":"0000-0002-5151-6424","position":3,"is_corresponding":false},{"id":1147313,"name":"Walfried Schneider","orcid":null,"position":4,"is_corresponding":false},{"id":1146902,"name":"Michael M. Wördehoff","orcid":"0000-0002-1591-0168","position":5,"is_corresponding":false},{"id":1146903,"name":"Melanie Schwarten","orcid":"0000-0001-8920-9668","position":6,"is_corresponding":false},{"id":583140,"name":"Dieter Willbold","orcid":"0000-0002-0065-7366","position":7,"is_corresponding":false},{"id":270829,"name":"Phanourios Tamamis","orcid":"0000-0002-3342-2651","position":8,"is_corresponding":false},{"id":1146904,"name":"Matthias Stoldt","orcid":"0000-0002-5060-4844","position":9,"is_corresponding":false},{"id":437644,"name":"Wolfgang Hoyer","orcid":"0000-0003-4301-5416","position":10,"is_corresponding":false},{"id":1147312,"name":"Laetitia Heid","orcid":null,"position":0,"is_corresponding":true}],"reference_count":64,"raw_metadata":null,"created_at":"2026-07-19T01:17:08.831117Z","pmid":"38223341","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":[]}