{"doi":"10.1074/mcp.m116.064675","title":"A Two-pronged Binding Mechanism of IgG to the Neonatal Fc Receptor Controls Complex Stability and IgG Serum Half-life","abstract":null,"journal":"Molecular & Cellular Proteomics","year":2017,"id":630298,"datarank":0.586803450814222,"base_score":3.912023005428146,"endowment":3.912023005428146,"self_citation_contribution":0.586803450814222,"citation_network_contribution":0.0,"self_endowment_contribution":0.586803450814222,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":49,"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":1632742,"name":"Angela Schoch","orcid":null,"position":1,"is_corresponding":false},{"id":1632743,"name":"Vincent Larraillet","orcid":null,"position":2,"is_corresponding":false},{"id":1632744,"name":"Maximiliane Hilger","orcid":null,"position":3,"is_corresponding":false},{"id":1632745,"name":"Tilman Schlothauer","orcid":null,"position":4,"is_corresponding":false},{"id":555632,"name":"Thomas Emrich","orcid":"0000-0003-1179-4697","position":5,"is_corresponding":false},{"id":597239,"name":"Kasper D. Rand","orcid":"0000-0002-6337-5489","position":6,"is_corresponding":false},{"id":1632741,"name":"Pernille Foged Jensen","orcid":"0000-0003-1495-6110","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"A Two-pronged Binding Mechanism of IgG to the Neonatal Fc Receptor Controls Complex Stability and IgG Serum Half-life","abstract":"The success of recombinant monoclonal immunoglobulins (IgG) is rooted in their ability to target distinct antigens with high affinity combined with an extraordinarily long serum half-life, typically around 3 weeks. The pharmacokinetics of IgGs is intimately linked to the recycling mechanism of the neonatal Fc receptor (FcRn). For long serum half-life of therapeutic IgGs, the highly pH-dependent interaction with FcRn needs to be balanced to allow efficient FcRn binding and release at slightly acidic pH and physiological pH, respectively. Some IgGs, like the antibody briakinumab has an unusually short half-life of ∼8 days. Here we dissect the molecular origins of excessive FcRn binding in therapeutic IgGs using a combination of hydrogen/deuterium exchange mass spectrometry and FcRn affinity chromatography. We provide experimental evidence for a two-pronged IgG-FcRn binding mechanism involving direct FcRn interactions with both the Fc region and the Fab regions of briakinumab, and correlate the occurrence of excessive FcRn binding to an unusually strong Fab-FcRn interaction.","is_dataset_classified":null,"base_score":3.912023005428146,"endowment":3.912023005428146,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"28062799","pmcid":"PMC5341005","openalex_id":"https://openalex.org/W2570172057","authors":[],"funders":[{"funder_name":"Natur og Univers, Det Frie Forskningsr?d","grant_id":"11-104058","title":null}],"total_grants":1,"fwci":2.709,"citation_percentile":0.89549494,"influential_citations":0,"citation_trend":[{"year":2017,"count":2},{"year":2018,"count":2},{"year":2019,"count":4},{"year":2020,"count":6},{"year":2021,"count":6},{"year":2022,"count":7},{"year":2023,"count":6},{"year":2024,"count":4},{"year":2025,"count":9},{"year":2026,"count":3}],"oa_status":"hybrid","license":"cc-by","oa_locations":[{"url":"https://www.mcponline.org/content/mcprot/16/3/451.full.pdf","host_type":"journal"},{"url":"https://www.mcponline.org/content/mcprot/16/3/451.full.pdf","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S1535947620324245?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S1535947620324245?httpAccept=text/plain","host_type":"publisher"},{"url":"https://syndication.highwire.org/content/doi/10.1074/mcp.M116.064675","host_type":"publisher"},{"url":"https://doi.org/10.1074/mcp.m116.064675","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/28062799","host_type":"repository"},{"url":"https://researchprofiles.ku.dk/da/publications/17c9172d-f7ef-40e1-8929-838b76eb8e52","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/5341005","host_type":"repository"},{"url":"https://curis.ku.dk/portal/da/publications/a-twopronged-binding-mechanism-of-igg-to-the-neonatal-fc-receptor-controls-complex-stability-and-igg-serum-halflife(17c9172d-f7ef-40e1-8929-838b76eb8e52).html","host_type":"repository"},{"url":"https://curis.ku.dk/ws/files/196136206/451.full.pdf","host_type":"repository"}],"fields_of_study":["Monoclonal and Polyclonal Antibodies Research","Glycosylation and Glycoproteins Research","T-cell and B-cell Immunology","Antibodies, Monoclonal","Antibodies, Monoclonal, Humanized","Binding Sites","Deuterium Exchange Measurement","Half-Life","Histocompatibility Antigens Class I","Humans","Hydrogen-Ion Concentration","Immunoglobulin G","Mass Spectrometry","Models, Molecular","Protein Binding","Protein Stability","Receptors, Fc"],"mesh_terms":["Antibodies, Monoclonal","Binding Sites","Half-Life","Humans","Hydrogen-Ion Concentration","Immunoglobulin G","Models, Molecular","Protein Binding","Receptors, Fc","Mass Spectrometry","Histocompatibility Antigens Class I","Deuterium Exchange Measurement","Protein Stability","Antibodies, Monoclonal, Humanized"],"keywords":["Neonatal Fc receptor","Mechanism (biology)","Receptor","Immunoglobulin G","Immunology","Antibody","Chemistry","Medicine","Biochemistry","Physics"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-05T20:51:16.019598Z","pmid":null,"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":[]}