UHM–ULM interactions in the RBM39–U2AF65 splicing-factor complex

摘要: RNA-binding protein 39 (RBM39) is a splicing factor and transcriptional co-activator of estrogen receptors Jun/AP-1, its function has been associated with malignant progression in number cancers. The C-terminal RRM domain RBM39 belongs to the U2AF homology motif family (UHM), which mediate protein–protein interactions through short tryptophan-containing peptide known as UHM-ligand (ULM). Here, crystal solution NMR structures RBM39-UHM domain, structure complex U2AF65-ULM, are reported. RBM39–U2AF65 interaction was confirmed by co-immunoprecipitation from human cell extracts, isothermal titration calorimetry chemical shift perturbation experiments purified proteins. When compared related complexes, such U2AF35–U2AF65 RBM39–SF3b155, RBM39-UHM–U2AF65-ULM reveals both common discriminating recognition elements UHM–ULM binding interface, providing rationale for specificity interactions. This study therefore establishes structural basis specific factors U2AF35, U2AF65, SF3b155, platform continued studies intermolecular governing disease-related alternative eukaryotic cells.