{"doi":"10.1016/j.mcpro.2022.100413","title":"Mass Spectrometry and Machine Learning Reveal Determinants of Client Recognition by Antiamyloid Chaperones","abstract":null,"journal":"Molecular & Cellular Proteomics","year":2022,"id":621435,"datarank":0.3453877639491069,"base_score":2.302585092994046,"endowment":2.302585092994046,"self_citation_contribution":0.3453877639491069,"citation_network_contribution":0.0,"self_endowment_contribution":0.3453877639491069,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1604737,"name":"Thibault Vosselman","orcid":"0000-0003-4699-5552","position":1,"is_corresponding":false},{"id":1604739,"name":"Axel Leppert","orcid":"0000-0001-6223-3350","position":2,"is_corresponding":false},{"id":144232,"name":"Astrid Gräslund","orcid":null,"position":3,"is_corresponding":false},{"id":204231,"name":"Hans Jörnvall","orcid":null,"position":4,"is_corresponding":false},{"id":1604741,"name":"Leopold L. Ilag","orcid":"0000-0003-3678-7100","position":5,"is_corresponding":false},{"id":1604743,"name":"Erik G. Marklund","orcid":"0000-0002-9804-5009","position":6,"is_corresponding":false},{"id":803850,"name":"Arne Elofsson","orcid":"0000-0002-7115-9751","position":7,"is_corresponding":false},{"id":795954,"name":"Jan Johansson","orcid":"0000-0002-8719-4703","position":8,"is_corresponding":false},{"id":488066,"name":"Cagla Sahin","orcid":"0000-0002-2889-5200","position":9,"is_corresponding":false},{"id":314460,"name":"Michael Landreh","orcid":"0000-0002-7958-4074","position":10,"is_corresponding":false},{"id":1082761,"name":"Nicklas Österlund","orcid":"0000-0003-0905-7911","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Mass Spectrometry and Machine Learning Reveal Determinants of Client Recognition by Antiamyloid Chaperones","abstract":"The assembly of proteins and peptides into amyloid fibrils is causally linked to serious disorders such as Alzheimer's disease. Multiple proteins have been shown to prevent amyloid formation in vitro and in vivo, ranging from highly specific chaperone-client pairs to completely nonspecific binding of aggregation-prone peptides. The underlying interactions remain elusive. Here, we turn to the machine learning-based structure prediction algorithm AlphaFold2 to obtain models for the nonspecific interactions of β-lactoglobulin, transthyretin, or thioredoxin 80 with the model amyloid peptide amyloid β and the highly specific complex between the BRICHOS chaperone domain of C-terminal region of lung surfactant protein C and its polyvaline target. Using a combination of native mass spectrometry (MS) and ion mobility MS, we show that nonspecific chaperoning is driven predominantly by hydrophobic interactions of amyloid β with hydrophobic surfaces in β-lactoglobulin, transthyretin, and thioredoxin 80, and in part regulated by oligomer stability. For C-terminal region of lung surfactant protein C, native MS and hydrogen-deuterium exchange MS reveal that a disordered region recognizes the polyvaline target by forming a complementary β-strand. Hence, we show that AlphaFold2 and MS can yield atomistic models of hard-to-capture protein interactions that reveal different chaperoning mechanisms based on separate ligand properties and may provide possible clues for specific therapeutic intervention.","is_dataset_classified":null,"base_score":2.302585092994046,"endowment":2.302585092994046,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"36115577","pmcid":"PMC9563204","openalex_id":"https://openalex.org/W4295941941","authors":[],"funders":[{"funder_name":"Novo Nordisk Fonden","grant_id":"NNF19OC0055700","title":null},{"funder_name":"Novo Nordisk Fonden","grant_id":"VR-2021-04744","title":null},{"funder_name":"Vetenskapsrådet","grant_id":"2013-08807","title":null},{"funder_name":"Vetenskapsrådet","grant_id":"VR-2016-06301","title":null},{"funder_name":"Vetenskapsrådet","grant_id":"2019-01961","title":null},{"funder_name":"Knut och Alice Wallenbergs Stiftelse","grant_id":"2020-04825","title":null},{"funder_name":"Cancerfonden","grant_id":"19 0480","title":null},{"funder_name":"Novo Nordisk Fonden","grant_id":"NNF18OC0055700","title":null},{"funder_name":"Knut and Alice Wallenberg Foundation","grant_id":"unidentified","title":"unidentified"},{"funder_name":"Stiftelsen Olle Engkvist Byggmästare","grant_id":"","title":null},{"funder_name":"Swedish e-Science Research Centre","grant_id":"","title":null},{"funder_name":"Karolinska Institute","grant_id":"","title":null}],"total_grants":12,"fwci":0.7058,"citation_percentile":0.66039835,"influential_citations":0,"citation_trend":[{"year":2023,"count":9}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"http://www.mcponline.org/article/S1535947622002213/pdf","host_type":"journal"},{"url":"http://www.mcponline.org/article/S1535947622002213/pdf","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S1535947622002213?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S1535947622002213?httpAccept=text/plain","host_type":"publisher"},{"url":"https://doi.org/10.1016/j.mcpro.2022.100413","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/36115577","host_type":"repository"},{"url":"http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-492116","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/9563204","host_type":"repository"},{"url":"https://researchprofiles.ku.dk/da/publications/ce9d7377-fc1e-49ed-8b81-186f2428932a","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC9563204","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC9563204?pdf=render","host_type":"Europe_PMC"},{"url":"http://dx.doi.org/10.1016/j.mcpro.2022.100413","host_type":""},{"url":"https://curis.ku.dk/ws/files/330734232/1_s2.0_S1535947622002213_main.pdf","host_type":""},{"url":"https://doi.org/https://doi.org/10.1016/j.mcpro.2022.100413","host_type":""}],"fields_of_study":["Protein Structure and Dynamics","Computational Drug Discovery Methods","Metabolomics and Mass Spectrometry Studies","0301 basic medicine","03 medical and health sciences","0303 health sciences","Humans","Amyloid","Amyloid beta-Peptides","Prealbumin","Deuterium","Ligands","Molecular Chaperones","Mass Spectrometry","Machine Learning","Thioredoxins","Lactoglobulins","Pulmonary Surfactant-Associated Proteins"],"mesh_terms":["Machine Learning","Amyloid","Deuterium","Humans","Lactoglobulins","Ligands","Prealbumin","Mass Spectrometry","Thioredoxins","Amyloid beta-Peptides","Molecular Chaperones","Pulmonary Surfactant-Associated Proteins"],"keywords":["Mass spectrometry","Chemistry","Computer science","Computational biology","Chromatography","Biology","Molecular chaperones","protein misfolding","Machine Learning","Structural Proteomics","Amyloid","Pulmonary Surfactant-Associated Proteins","Cell- och molekylärbiologi","BETA","Lactoglobulins","Ligands","Biochemistry","BINDING-SITES","GAS-PHASE","Thioredoxins","Humans","Prealbumin","Biokemi","Molecular Biology","PROSURFACTANT PROTEIN-C","Molekylärbiologi","Amyloid beta-Peptides","Research","ION MOBILITY","AMYLOID FIBRILLATION","AGGREGATION","TRANSTHYRETIN","Deuterium","INSIGHTS","BRICHOS DOMAIN","Cell and Molecular Biology"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. 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