{"doi":"10.1002/prot.26350","title":"IGF‐dependent dynamic modulation of a protease cleavage site in the intrinsically disordered linker domain of human <scp>IGFBP2</scp>","abstract":"Functional regulation via conformational dynamics is well known in structured proteins but less well characterized in intrinsically disordered proteins and their complexes. Using NMR spectroscopy, we have identified a dynamic regulatory mechanism in the human insulin-like growth factor (IGF) system involving the central, intrinsically disordered linker domain of human IGF-binding protein-2 (hIGFBP2). The bioavailability of IGFs is regulated by the proteolysis of IGF-binding proteins. In the case of hIGFBP2, the linker domain (L-hIGFBP2) retains its intrinsic disorder upon binding IGF-1, but its dynamics are significantly altered, both in the IGF binding region and distantly located protease cleavage sites. The increase in flexibility of the linker domain upon IGF-1 binding may explain the IGF-dependent modulation of proteolysis of IGFBP2 in this domain. As IGF homeostasis is important for cell growth and function, and its dysregulation is a key contributor to several cancers, our findings open up new avenues for the design of IGFBP analogs inhibiting IGF-dependent tumors.","journal":"Proteins Structure Function and Bioinformatics","year":2022,"id":283400,"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":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9551,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":833018,"name":"Divya Shet","orcid":"0000-0002-2778-156X","position":1,"is_corresponding":false},{"id":833420,"name":"Shahid Malik","orcid":null,"position":2,"is_corresponding":false},{"id":729145,"name":"Monalisa Swain","orcid":null,"position":3,"is_corresponding":false},{"id":833019,"name":"Hanudatta S. Atreya","orcid":"0000-0003-0200-7372","position":4,"is_corresponding":false},{"id":833020,"name":"Charles A. Galea","orcid":"0000-0003-0485-7709","position":5,"is_corresponding":false},{"id":833421,"name":"Mark G. Slomiany","orcid":null,"position":6,"is_corresponding":false},{"id":589010,"name":"Steven A Rosenzweig","orcid":"0000-0002-7022-6086","position":7,"is_corresponding":false},{"id":347614,"name":"Briony E. Forbes","orcid":"0000-0003-4360-9927","position":8,"is_corresponding":false},{"id":833021,"name":"Raymond S. Norton","orcid":"0000-0001-8893-0584","position":9,"is_corresponding":false},{"id":833022,"name":"Somnath Mondal","orcid":"0000-0002-5657-8077","position":10,"is_corresponding":false},{"id":833419,"name":"Garima Jaipuria","orcid":null,"position":0,"is_corresponding":true}],"reference_count":73,"raw_metadata":null,"created_at":"2026-07-19T00:29:28.452697Z","pmid":"35443068","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":[]}