{"doi":"10.1074/jbc.m000010200","title":"Mechanisms for High Affinity Mannose 6-Phosphate Ligand Binding to the Insulin-like Growth Factor II/Mannose 6-Phosphate Receptor","abstract":null,"journal":"Journal of Biological Chemistry","year":2000,"id":685703,"datarank":0.5897738449086489,"base_score":3.9318256327243257,"endowment":3.9318256327243257,"self_citation_contribution":0.5897738449086489,"citation_network_contribution":0.0,"self_endowment_contribution":0.5897738449086489,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":50,"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":1791475,"name":"Richard G. MacDonald","orcid":null,"position":1,"is_corresponding":false},{"id":191592,"name":"James C. Byrd","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Mechanisms for High Affinity Mannose 6-Phosphate Ligand Binding to the Insulin-like Growth Factor II/Mannose 6-Phosphate Receptor","abstract":"The two mannose 6-phosphate (Man-6-P) binding domains of the insulin-like growth factor II/mannose 6-phosphate receptor (Man-6-P/IGF2R), located in extracytoplasmic repeats 1-3 and 7-9, are capable of binding Man-6-P with low affinity and glycoproteins that contain more than one Man-6-P residue with high affinity. High affinity multivalent ligand binding sites could be formed through two possible mechanisms: the interaction of two Man-6-P binding domains within one Man-6-P/IGF2R molecule or by receptor oligomerization. To discriminate between these mechanisms, truncated FLAG epitope-tagged Man-6-P/IGF2R constructs, containing one or both of the Man-6-P binding domains, were expressed in 293T cells, and characterized for binding of pentamannose phosphate-bovine serum albumin (PMP-BSA), a pseudoglycoprotein bearing multiple Man-6-P residues. A construct containing all 15 repeats of the Man-6-P/IGF2R extracytoplasmic domain bound PMP-BSA with the same affinity as the full-length receptor (K(d) = 0.54 nm) with a curvilinear Scatchard plot. The presence of excess unlabeled PMP-BSA increased the dissociation rate of pre-formed (125)I-PMP-BSA/receptor complexes, suggesting negative cooperativity in multivalent ligand binding and affirming the role of multiple Man-6-P/IGF2R binding domains in forming high affinity binding sites. Truncated receptors containing only one Man-6-P binding domain and mutant receptor constructs, containing an Arg(1325) --> Ala mutation that eliminates binding to the repeats 7-9 binding domain, formed high affinity PMP-BSA binding, but with reduced stoichiometries. Collectively, these observations suggest that alignment of Man-6-P binding domains of separate Man-6-P/IGF2R molecules is responsible for the formation of high affinity Man-6-P binding sites and provide functional evidence for Man-6-P/IGF2R oligomerization.","is_dataset_classified":null,"base_score":3.9318256327243257,"endowment":3.9318256327243257,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"10764735","pmcid":null,"openalex_id":"https://openalex.org/W2131380785","authors":[],"funders":[{"funder_name":"NIDDK NIH HHS","grant_id":"DK44212","title":null}],"total_grants":1,"fwci":1.5363,"citation_percentile":0.82620785,"influential_citations":0,"citation_trend":[{"year":2012,"count":3},{"year":2013,"count":1},{"year":2015,"count":5},{"year":2016,"count":2},{"year":2017,"count":1},{"year":2018,"count":3},{"year":2019,"count":1},{"year":2020,"count":2},{"year":2023,"count":1},{"year":2024,"count":1},{"year":2026,"count":2}],"oa_status":"hybrid","license":"cc-by","oa_locations":[{"url":"https://doi.org/10.1074/jbc.m000010200","host_type":"journal"},{"url":"https://doi.org/10.1074/jbc.m000010200","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S002192581980114X?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S002192581980114X?httpAccept=text/plain","host_type":"publisher"},{"url":"https://syndication.highwire.org/content/doi/10.1074/jbc.M000010200","host_type":"publisher"},{"url":"https://pubmed.ncbi.nlm.nih.gov/10764735","host_type":"repository"},{"url":"http://www.jbc.org/article/S002192581980114X/pdf","host_type":"Unpaywall"}],"fields_of_study":["Glycosylation and Glycoproteins Research","Erythrocyte Function and Pathophysiology","Blood disorders and treatments","Cell Line","Cytoplasm","Humans","Ligands","Mannosephosphates","Protein Binding","Receptor, IGF Type 2"],"mesh_terms":["Cell Line","Cytoplasm","Humans","Ligands","Mannosephosphates","Protein Binding","Receptor, IGF Type 2"],"keywords":["Insulin-like growth factor 2 receptor","Mannose 6-phosphate","Receptor","Chemistry","Mannose","Binding site","Biochemistry","Cooperative binding","Ligand (biochemistry)","Cooperativity","Plasma protein binding","Growth factor","Insulin-like growth factor 1 receptor"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Reduced inequalities"},{"sdg_number":0,"sdg_label":"Peace, Justice and strong institutions"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-18T17:23:00.891073Z","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":[]}