{"doi":"10.1016/j.jsb.2025.108247","title":"Structural insights into IMP2 dimerization and RNA binding","abstract":"IGF2BP2 (IMP2) is an RNA-binding protein that contributes to tumorigenesis and metabolic disorders. Structural studies focused on individual IMP2 domains have provided important mechanistic insights into IMP2 function; however, structural information on full-length IMP2 is lacking but necessary to understand how to target IMP2 activity in drug discovery. In this study, we investigated the behavior of full-length IMP2 and the influence of RNA binding using biophysical and structural methods including mass photometry, hydrogen-deuterium exchange coupled to mass spectrometry (HDX-MS), and small angle x-ray scattering (SAXS). We found that full-length IMP2 forms multiple oligomeric states but predominantly adopts a dimeric conformation. Molecular models derived from SAXS data suggest the dimer is formed in a head-to-tail orientation by the KH34 and RRM1 domains. Upon RNA binding, IMP2 forms a pseudo-symmetric dimer different from its apo/RNA-free state. We also found that the formation of IMP2 oligomeric species, which includes dimers and higher-order oligomers, is sensitive to ionic strength and RNA binding. Our findings provide the first insight into the structural properties of full-length IMP2, which may lead to novel opportunities for disrupting its function.","journal":"Journal of Structural Biology","year":2025,"id":546874,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.961,"is_data_producer":false,"deposit_databanks":null,"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":343815,"name":"Paola Munoz‐Tello","orcid":"0000-0002-5225-1907","position":1,"is_corresponding":false},{"id":566978,"name":"Timothy R. O’Leary","orcid":"0000-0001-7865-7705","position":2,"is_corresponding":false},{"id":753719,"name":"Xiaoyu Yu","orcid":"0000-0003-0549-9560","position":3,"is_corresponding":false},{"id":939142,"name":"Mithun Nag Karadi Giridhar","orcid":"0000-0003-0520-5921","position":4,"is_corresponding":false},{"id":1409347,"name":"Alexander D. Hondros","orcid":"0000-0002-2104-9693","position":5,"is_corresponding":false},{"id":1098825,"name":"Althea Hansel-Harris","orcid":"0000-0001-7064-1119","position":6,"is_corresponding":false},{"id":233718,"name":"Stefano Forli","orcid":"0000-0002-5964-7111","position":7,"is_corresponding":false},{"id":282828,"name":"Patrick R. Griffin","orcid":"0000-0002-3404-690X","position":8,"is_corresponding":false},{"id":282829,"name":"Douglas J. Kojetin","orcid":"0000-0001-8058-6168","position":9,"is_corresponding":false},{"id":744901,"name":"Raktim N. Roy","orcid":"0000-0001-8410-5819","position":10,"is_corresponding":false},{"id":109508,"name":"Michalina Janiszewska","orcid":"0000-0002-8592-5146","position":11,"is_corresponding":false},{"id":1330860,"name":"Stephen A Zorc","orcid":null,"position":0,"is_corresponding":true}],"reference_count":54,"raw_metadata":null,"created_at":"2026-07-19T02:53:36.567932Z","pmid":"40946981","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":[]}