{"doi":"10.3390/ijms24076477","title":"HED, a Human-Engineered Domain, Confers a Unique Fc-Binding Activity to Produce a New Class of Humanized Antibody-like Molecules","abstract":"Our laboratory has identified and developed a unique human-engineered domain (HED) structure that was obtained from the human Alpha-2-macroglobulin receptor-associated protein based on the three-dimensional structure of the Z-domain derived from Staphylococcal protein A. This HED retains µM binding activity to the human IgG1CH2-CH3 elbow region. We determined the crystal structure of HED in association with IgG1's Fc. This demonstrated that HED preserves the same three-bundle helix structure and Fc-interacting residues as the Z domain. HED was fused to the single chain variable fragment (scFv) of mAb 4D5 to produce an antibody-like protein capable of interacting with the p185Her2/neu ectodomain and the Fc of IgG. When further fused with murine IFN-γ (mIFN-γ) at the carboxy terminus, the novel species exhibited antitumor efficacy in vivo in a mouse model of human breast cancer. The HED is a novel platform for the therapeutic utilization of engineered proteins to alleviate human disease.","journal":"International Journal of Molecular Sciences","year":2023,"id":404424,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9526,"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":624955,"name":"Peeyush N. Goel","orcid":null,"position":1,"is_corresponding":false},{"id":458634,"name":"Zheng Cai","orcid":"0009-0007-8000-3912","position":2,"is_corresponding":false},{"id":353010,"name":"Yasuhiro Nagai","orcid":"0000-0003-1472-4213","position":3,"is_corresponding":false},{"id":785010,"name":"Lian Lam","orcid":"0000-0001-9700-4988","position":4,"is_corresponding":false},{"id":481163,"name":"Arabinda Samanta","orcid":"0009-0007-6252-5282","position":5,"is_corresponding":false},{"id":1182777,"name":"Meiqing Ji","orcid":null,"position":6,"is_corresponding":false},{"id":429813,"name":"Hongtao Zhang","orcid":"0000-0001-9173-0049","position":7,"is_corresponding":false},{"id":763606,"name":"Mark I. Greene","orcid":"0000-0001-6589-9668","position":8,"is_corresponding":false},{"id":1182287,"name":"Zhiqiang Zhu","orcid":"0000-0002-0280-3232","position":0,"is_corresponding":true}],"reference_count":48,"raw_metadata":null,"created_at":"2026-07-19T01:20:44.591715Z","pmid":"37047449","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":[]}