{"doi":"10.1016/j.jbc.2025.110253","title":"Molecular basis for presentation of N-myristoylated peptides by the chicken YF1∗7.1 molecule","abstract":"Major histocompatibility complex I (MHC-I) and MHC-I-like molecules play a central role in mediating immunity. Through their conservation across all taxa of jawed vertebrates, the MHC-I-like proteins have adapted to present non-peptidic antigens to distinct T cell populations. While our understanding of the structure-function relationship of MHC-I and MHC-I-like molecules in humans and mice is well established, the nature of the antigens presented by MHC-I- like molecules in \"non-model\" species remains unclear. Here, using a mammalian recombinant expression system combined with mass spectrometry approaches, we identified N-myristoylated peptides as endogenous ligands for the chicken MHC-I-like protein YF1∗7.1. Given the importance of N-myristoylation in viral pathogenesis, we determined the crystal structure of YF1∗7.1 in complex with two N-myristoylated peptides derived from Marek's disease virus (MDV), demonstrating the molecular basis that underpins the presentation of N-myristoylated peptides from MDV, a highly contagious and fatal viral neoplastic disease in chickens. Thus, the identified ligands are distinct from unmodified peptides found in classical MHC-I and -II as well as diverse amphipathic lipids captured by CD1 proteins. Collectively, our study lays the foundation for further molecular and functional characterization of YF1∗7.1 and more broadly of the role of the MHC-I encoded by the MHC-Y gene cluster in protection against highly contagious viral neoplastic diseases in chickens.","journal":"Journal of Biological Chemistry","year":2025,"id":552877,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":1,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9542,"is_data_producer":true,"deposit_databanks":{"PDB":["9EB2","9EB4","9EB5","9EB6","9EB3"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":314930,"name":"Tan‐Yun Cheng","orcid":"0000-0002-5178-6985","position":1,"is_corresponding":false},{"id":877573,"name":"Carl J. H. Wang","orcid":"0000-0003-4564-3125","position":2,"is_corresponding":false},{"id":756318,"name":"Thinh-Phat Cao","orcid":"0000-0001-9387-5460","position":3,"is_corresponding":false},{"id":1449194,"name":"Raghavendra Sashi Krishna Nagampalli","orcid":"0000-0001-7382-130X","position":4,"is_corresponding":false},{"id":737860,"name":"Komagal Kannan Sivaraman","orcid":null,"position":5,"is_corresponding":false},{"id":252300,"name":"Ildiko Van Rhijn","orcid":"0000-0002-1446-5701","position":6,"is_corresponding":false},{"id":256186,"name":"Jamie Rossjohn","orcid":"0000-0002-2020-7522","position":7,"is_corresponding":false},{"id":312635,"name":"D. Branch Moody","orcid":"0000-0003-2306-3058","position":8,"is_corresponding":false},{"id":293171,"name":"Jérôme Le Nours","orcid":"0000-0002-2221-7636","position":9,"is_corresponding":false},{"id":867090,"name":"Yogesh Khandokar","orcid":"0000-0002-4630-8508","position":0,"is_corresponding":true}],"reference_count":59,"raw_metadata":null,"created_at":"2026-07-19T02:54:37.527189Z","pmid":"40412526","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":[]}