{"display":true,"structure":{"allele":{"alpha":{"identifier":"ipd-imgt:HLA34091","locus":"hla-a","match_type":"histo:exact","name":"HLA-A*68:01","slug":"hla_a_68_01","species_stem":"hla"},"beta":{}},"assemblies":{"1":{"assembly_name":"6wna_1","chains":["A","B","H","C"],"downloaded_at":"2022-11-09T14:39:02.086860"}},"assembly_count":null,"assigned_chains":{"beta2m":{"chains":["B"],"match_type":"histo:assign_chains","score":1.0,"sequence":"IQRTPKIQVYSRHPAENGKSNFLNCYVSGFHPSDIEVDLLKNGERIEKVEHSDLSFSKDWSFYLLYYTEFTPTEKDEYACRVNHVTLSQPKIVKWDRDM"},"fcrn":{"chains":["A"],"match_type":"histo:assign_chains","score":0.99,"sequence":"HLSLLYHLTAVSSPAPGTPAFWVSGWLGPQQYLSYNSLRGEAEPCGAWVWENQVSWYWEKETTDLRIKEKLFLEAFKALGGKGPYTLQGLLGCELGPDNTSVPTAKFALNGEEFMNFDLKQGTWGGDWPEALAISQRWQQQDKAANKELTFLLFSCPHRLREHLERGRGNLEWKEPPSMRLKARPSSPGFSVLTCSAFSFYPPELQLRFLRNGLAAGTGQGDFGPNSDGSFHASSSLTVKSGDEHHYCCIVQHAGLAQPLRVEL"},"ig_heavy_chain_gamma":{"chains":["H"],"match_type":"histo:override","sequence":"PSVFLFPPKPKDTLYITREPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTFPPEQEEMTKNQVSLRCLVKGFYPSDIAVEWESNGQPENNYKTTKPVLDSDGSFRLESRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLS"},"note":"rule needed for ig_heavy chain?"},"chronology":{"deposition_date":"2020-04-22","deposition_year":2020,"release_date":"2021-09-15","release_year":2021,"revision_date":"2021-09-22","revision_year":2021},"class":"class_i","classical":false,"complex_type":"fcrn_with_beta2m_and_ig_heavy_chain_gamma","components":["fcrn","beta2m","ig_heavy_chain_gamma"],"experimental_method":"X-ray diffraction","facets":{},"ligands":[],"locus":"hla-a","manually_edited":{},"missing_residues":[],"page_title":"6WNA | Non-classical MHC Class I molecule Feonatal Fc receptor (FcRn) with Ig heavy chain gamma","pdb_code":"6wna","pdb_title":"Next generation monomeric igg4 fc","peptide":{"actual_sequence":null,"epitope_info":{},"features":[],"full_sequence":null,"gap_info":{},"gapped_sequence":null,"length":{"numeric":null,"text":null},"unnatural_amino_acids":[]},"publication":{"abstract":"In a biologic therapeutic landscape that requires versatility in targeting specificity, valency and half-life modulation, the monomeric Fc fusion platform holds exciting potential for the creation of a class of monovalent protein therapeutics that includes fusion proteins and bispecific targeting molecules. Here we report a structure-guided approach to engineer monomeric Fc molecules to adapt multiple versions of half-life extension modifications. Co-crystal structures of these monomeric Fc variants with Fc neonatal receptor (FcRn) shed light into the binding interactions that could serve as a guide for engineering the half-life of antibody Fc fragments. These engineered monomeric Fc molecules also enabled the generation of a novel monovalent bispecific molecular design, which translated the FcRn binding enhancement to improvement of in vivo serum half-life.","bibjson":{"author":[{"initials":"L","lastname":"Shan","name":"Shan L"},{"initials":"NV","lastname":"Dyk","name":"Dyk NV"},{"initials":"N","lastname":"Haskins","name":"Haskins N"},{"initials":"KM","lastname":"Cook","name":"Cook KM"},{"initials":"KL","lastname":"Rosenthal","name":"Rosenthal KL"},{"initials":"R","lastname":"Mazor","name":"Mazor R"},{"initials":"S","lastname":"Dragulin-Otto","name":"Dragulin-Otto S"},{"initials":"Y","lastname":"Jiang","name":"Jiang Y"},{"initials":"H","lastname":"Wu","name":"Wu H"},{"initials":"WF","lastname":"Dall'Acqua","name":"Dall'Acqua WF"},{"initials":"MJ","lastname":"Borrok","name":"Borrok MJ"},{"initials":"MM","lastname":"Damschroder","name":"Damschroder MM"},{"initials":"V","lastname":"Oganesyan","name":"Oganesyan V"}],"identifier":[{"id":"10.1038/s42003-021-02565-5","type":"doi"},{"id":"34497355","type":"pubmed"}],"issue":["1"],"journal":{"iso_abbreviation":"Commun Biol","name":""},"pages":["1048"],"title":"In vivo pharmacokinetic enhancement of monomeric Fc and monovalent bispecific designs through structural guidance.","type":"article","url":"https://www.nature.com/articles/s42003-021-02565-5","volume":["4"],"year":[2021]},"in_pmc":"N","in_pmce":"Y","open_access":"Y"},"resolution":"2.40","same_as":{"pdbe":{"url":"https://www.ebi.ac.uk/pdbe/entry/pdb/6wna"},"rcsb":{"url":"https://www.rcsb.org/structure/6wna"}},"species":{"common_name":"Human","match_type":"histo:assign_species","scientific_name":"Homo sapiens","slug":"homo_sapiens"},"tcr":null,"title":"Non-classical MHC Class I molecule Feonatal Fc receptor (FcRn) with Ig heavy chain gamma at 2.40Å resolution","unique_chain_count":3}}