{"doi":"10.1084/jem.20041890","title":"Structural basis for the function and regulation of the receptor protein tyrosine phosphatase CD45","abstract":"<jats:p>CD45 is the prototypic member of transmembrane receptor-like protein tyrosine phosphatases (RPTPs) and has essential roles in immune functions. The cytoplasmic region of CD45, like many other RPTPs, contains two homologous protein tyrosine phosphatase domains, active domain 1 (D1) and catalytically impaired domain 2 (D2). Here, we report crystal structure of the cytoplasmic D1D2 segment of human CD45 in native and phosphotyrosyl peptide-bound forms. The tertiary structures of D1 and D2 are very similar, but doubly phosphorylated CD3ζ immunoreceptor tyrosine-based activation motif peptide binds only the D1 active site. The D2 “active site” deviates from the other active sites significantly to the extent that excludes any possibility of catalytic activity. The relative orientation of D1 and D2 is very similar to that observed in leukocyte common antigen–related protein with both active sites in an open conformation and is restrained through an extensive network of hydrophobic interactions, hydrogen bonds, and salt bridges. This crystal structure is incompatible with the wedge model previously suggested for CD45 regulation.</jats:p>","journal":"The Journal of Experimental Medicine","year":2005,"id":676860,"datarank":0.7050720548688626,"base_score":4.700480365792417,"endowment":4.700480365792417,"self_citation_contribution":0.7050720548688626,"citation_network_contribution":0.0,"self_endowment_contribution":0.7050720548688626,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":109,"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":837961,"name":"Florence Poy","orcid":null,"position":1,"is_corresponding":false},{"id":1615497,"name":"Haruo Saito","orcid":null,"position":2,"is_corresponding":false},{"id":1768491,"name":"Christin A. Frederick","orcid":null,"position":3,"is_corresponding":false},{"id":1768484,"name":"Hyun-Joo Nam","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Structural basis for the function and regulation of the receptor protein tyrosine phosphatase CD45","abstract":"<jats:p>CD45 is the prototypic member of transmembrane receptor-like protein tyrosine phosphatases (RPTPs) and has essential roles in immune functions. The cytoplasmic region of CD45, like many other RPTPs, contains two homologous protein tyrosine phosphatase domains, active domain 1 (D1) and catalytically impaired domain 2 (D2). Here, we report crystal structure of the cytoplasmic D1D2 segment of human CD45 in native and phosphotyrosyl peptide-bound forms. The tertiary structures of D1 and D2 are very similar, but doubly phosphorylated CD3ζ immunoreceptor tyrosine-based activation motif peptide binds only the D1 active site. The D2 “active site” deviates from the other active sites significantly to the extent that excludes any possibility of catalytic activity. The relative orientation of D1 and D2 is very similar to that observed in leukocyte common antigen–related protein with both active sites in an open conformation and is restrained through an extensive network of hydrophobic interactions, hydrogen bonds, and salt bridges. This crystal structure is incompatible with the wedge model previously suggested for CD45 regulation.</jats:p>","is_dataset_classified":null,"base_score":4.700480365792417,"endowment":4.700480365792417,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"15684325","pmcid":"PMC2213029","openalex_id":"https://openalex.org/W2134799471","authors":[],"funders":[{"funder_name":"NCI NIH HHS","grant_id":"T32-CA09361","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"R01-GM53415","title":null},{"funder_name":"NCI NIH HHS","grant_id":"T32 CA009361","title":null},{"funder_name":"National Institutes of Health","grant_id":"5R01GM053415-07","title":"RECEPTOR LINKED PROTEIN TYROSINE PHOSPHATASES"},{"funder_name":"National Institutes of Health","grant_id":"5T32CA009361-18","title":"MOLECULAR ANALYSIS OF NEOPLASTIC DISEASE"}],"total_grants":5,"fwci":3.3252,"citation_percentile":0.9285231,"influential_citations":0,"citation_trend":[{"year":2012,"count":9},{"year":2013,"count":5},{"year":2014,"count":4},{"year":2015,"count":5},{"year":2016,"count":1},{"year":2017,"count":3},{"year":2018,"count":3},{"year":2019,"count":5},{"year":2020,"count":2},{"year":2021,"count":3},{"year":2022,"count":6},{"year":2023,"count":8},{"year":2024,"count":3},{"year":2025,"count":2},{"year":2026,"count":2}],"oa_status":"bronze","license":"http://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/ (http://creativecommons.org/licenses/by-nc-sa/4.0/) ).","oa_locations":[{"url":"https://rupress.org/jem/article-pdf/201/3/441/1153346/jem2013441.pdf","host_type":"journal"},{"url":"https://rupress.org/jem/article-pdf/201/3/441/1153346/jem2013441.pdf","host_type":"publisher"},{"url":"https://rupress.org/jem/article-pdf/201/3/441/1716424/jem2013441.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1084/jem.20041890","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/15684325","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/2213029","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC2213029","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC2213029?pdf=render","host_type":"Europe_PMC"},{"url":"http://jem.rupress.org/content/201/3/441.full.pdf","host_type":""},{"url":"http://dx.doi.org/10.1084/jem.20041890","host_type":""},{"url":"https://dx.doi.org/10.1084/jem.20041890","host_type":""}],"fields_of_study":["Protein Tyrosine Phosphatases","Galectins and Cancer Biology","Glycosylation and Glycoproteins Research","0301 basic medicine","0303 health sciences","03 medical and health sciences","Amino Acid Sequence","Animals","Binding Sites","CD3 Complex","Crystallography, X-Ray","Humans","Leukocyte Common Antigens","Models, Molecular","Molecular Sequence Data","Phosphopeptides","Protein Isoforms","Protein Structure, Tertiary","Sequence Alignment"],"mesh_terms":["Amino Acid Sequence","Animals","Binding Sites","Humans","Models, Molecular","Molecular Sequence Data","Phosphopeptides","Sequence Alignment","Protein Tyrosine Phosphatases","CD3 Complex","Protein Structure, Tertiary","Leukocyte Common Antigens","Crystallography, X-Ray","Protein Isoforms"],"keywords":["Protein tyrosine phosphatase","Active site","Tyrosine","Chemistry","Phosphatase","Transmembrane protein","Immunoreceptor tyrosine-based activation motif","Transmembrane domain","Phosphorylation","SH2 domain","Protein structure","Biochemistry","Receptor tyrosine kinase","Cytoplasm","Binding site","Receptor","Biology","Enzyme","Models, Molecular","Phosphopeptides","Binding Sites","CD3 Complex","Molecular Sequence Data","Crystallography, X-Ray","Article","Protein Structure, Tertiary","Animals","Humans","Leukocyte Common Antigens","Protein Isoforms","Amino Acid Sequence","Protein Tyrosine Phosphatases","Sequence Alignment"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-17T03:14:37.057580Z","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":[]}