{"doi":"10.1016/j.jbc.2023.104729","title":"Mapping N- to C-terminal allosteric coupling through disruption of a putative CD74 activation site in D-dopachrome tautomerase","abstract":"The macrophage migration inhibitory factor (MIF) protein family consists of MIF and D-dopachrome tautomerase (also known as MIF-2). These homologs share 34% sequence identity while maintaining nearly indistinguishable tertiary and quaternary structure, which is likely a major contributor to their overlapping functions, including the binding and activation of the cluster of differentiation 74 (CD74) receptor to mediate inflammation. Previously, we investigated a novel allosteric site, Tyr99, that modulated N-terminal catalytic activity in MIF through a \"pathway\" of dynamically coupled residues. In a comparative study, we revealed an analogous allosteric pathway in MIF-2 despite its unique primary sequence. Disruptions of the MIF and MIF-2 N termini also diminished CD74 activation at the C terminus, though the receptor activation site is not fully defined in MIF-2. In this study, we use site-directed mutagenesis, NMR spectroscopy, molecular simulations, in vitro and in vivo biochemistry to explore the putative CD74 activation region of MIF-2 based on homology to MIF. We also confirm its reciprocal structural coupling to the MIF-2 allosteric site and N-terminal enzymatic site. Thus, we provide further insight into the CD74 activation site of MIF-2 and its allosteric coupling for immunoregulation.","journal":"Journal of Biological Chemistry","year":2023,"id":351051,"datarank":0.4611116842694989,"base_score":2.302585092994046,"endowment":2.302585092994046,"self_citation_contribution":0.3453877639491069,"citation_network_contribution":0.11572392032039196,"self_endowment_contribution":0.3453877639491069,"citer_contribution":0.11572392032039196,"corpus_percentile":null,"corpus_rank":null,"citation_count":9,"citer_count":6,"citers_with_citation_signal":5,"citers_with_endowment":5,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9498,"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":739606,"name":"Vinnie Widjaja","orcid":"0000-0002-3190-5633","position":1,"is_corresponding":false},{"id":1024278,"name":"Gregory W. Kyro","orcid":"0000-0002-0095-8548","position":2,"is_corresponding":false},{"id":676449,"name":"Brandon Allen","orcid":"0000-0002-5512-1892","position":3,"is_corresponding":false},{"id":424665,"name":"Pragnya Das","orcid":"0000-0003-4818-2387","position":4,"is_corresponding":false},{"id":1047962,"name":"Varsha Prahaladan","orcid":null,"position":5,"is_corresponding":false},{"id":339237,"name":"Vineet Bhandari","orcid":"0000-0002-4900-6636","position":6,"is_corresponding":false},{"id":340258,"name":"Elias Lolis","orcid":"0000-0002-7902-7868","position":7,"is_corresponding":false},{"id":340256,"name":"Víctor S. Batista","orcid":"0000-0002-3262-1237","position":8,"is_corresponding":false},{"id":340257,"name":"George P. Lisi","orcid":"0000-0001-8878-5655","position":9,"is_corresponding":false},{"id":1095765,"name":"Emily Chen","orcid":"0000-0003-3308-7125","position":0,"is_corresponding":true}],"reference_count":42,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:12:41.740237Z","pmid":"37080391","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":[]}