5cxt
From Proteopedia
Crystal structure of a RNA-binding protein 39 (RBM39) in complex with fragment of splicing factor (U2AF) from Unknown at 2.20 A resolution
Structural highlights
Function[RBM39_MOUSE] Transcriptional coactivator for steroid nuclear receptors ESR1/ER-alpha and ESR2/ER-beta, and JUN/AP-1. May be involved in pre-mRNA splicing process.[1] [U2AF2_MOUSE] Necessary for the splicing of pre-mRNA. Induces cardiac troponin-T (TNNT2) pre-mRNA exon inclusion in muscle. Regulates the TNNT2 exon 5 inclusion through competition with MBNL1. Binds preferentially to a single-stranded structure within the polypyrimidine tract of TNNT2 intron 4 during spliceosome assembly. Required for the export of mRNA out of the nucleus, even if the mRNA is encoded by an intron-less gene. Represses the splicing of MAPT/Tau exon 10 (By similarity). Publication Abstract from PubMedRNA-binding protein 39 (RBM39) is a splicing factor and a transcriptional co-activator of estrogen receptors and Jun/AP-1, and its function has been associated with malignant progression in a number of cancers. The C-terminal RRM domain of RBM39 belongs to the U2AF homology motif family (UHM), which mediate protein-protein interactions through a short tryptophan-containing peptide known as the UHM-ligand motif (ULM). Here, crystal and solution NMR structures of the RBM39-UHM domain, and the crystal structure of its complex with U2AF65-ULM, are reported. The RBM39-U2AF65 interaction was confirmed by co-immunoprecipitation from human cell extracts, by isothermal titration calorimetry and by NMR chemical shift perturbation experiments with the purified proteins. When compared with related complexes, such as U2AF35-U2AF65 and RBM39-SF3b155, the RBM39-UHM-U2AF65-ULM complex reveals both common and discriminating recognition elements in the UHM-ULM binding interface, providing a rationale for the known specificity of UHM-ULM interactions. This study therefore establishes a structural basis for specific UHM-ULM interactions by splicing factors such as U2AF35, U2AF65, RBM39 and SF3b155, and a platform for continued studies of intermolecular interactions governing disease-related alternative splicing in eukaryotic cells. UHM-ULM interactions in the RBM39-U2AF65 splicing-factor complex.,Stepanyuk GA, Serrano P, Peralta E, Farr CL, Axelrod HL, Geralt M, Das D, Chiu HJ, Jaroszewski L, Deacon AM, Lesley SA, Elsliger MA, Godzik A, Wilson IA, Wuthrich K, Salomon DR, Williamson JR Acta Crystallogr D Struct Biol. 2016 Apr 1;72(Pt 4):497-511. doi:, 10.1107/S2059798316001248. Epub 2016 Mar 24. PMID:27050129[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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