5CXT

Crystal structure of a RNA-binding protein 39 (RBM39) in complex with fragment of splicing factor (U2AF) from Unknown at 2.20 A resolution

Summary for 5CXT

• Entry DOI: 10.2210/pdb5cxt/pdb
• Descriptor: RNA-binding protein 39, Splicing factor U2AF 65 kDa subunit (3 entities in total)
• Functional Keywords: rbm39linker (pf15519), rna recognition motif (pf13893), structural genomics, joint center for structural genomics, jcsg, protein structure initiative, psi-biology, rna binding protein, partnership for t-cell biology, tcell
• Biological source: Mus musculus (Mouse); More
• Cellular location: Nucleus : Q8VH51 P26369
• Total number of polymer chains: 18
• Total formula weight: 144552.62

Authors

Joint Center for Structural Genomics (JCSG),Partnership for T-Cell Biology (TCELL) (deposition date: 2015-07-29, release date: 2015-10-14, Last modification date: 2023-09-27)

Primary citation

Stepanyuk, G.A.,Serrano, P.,Peralta, E.,Farr, C.L.,Axelrod, H.L.,Geralt, M.,Das, D.,Chiu, H.J.,Jaroszewski, L.,Deacon, A.M.,Lesley, S.A.,Elsliger, M.A.,Godzik, A.,Wilson, I.A.,Wuthrich, K.,Salomon, D.R.,Williamson, J.R.
UHM-ULM interactions in the RBM39-U2AF65 splicing-factor complex.
Acta Crystallogr D Struct Biol, 72:497-511, 2016

PubMed Abstract: RNA-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.

PubMed: 27050129
DOI: 10.1107/S2059798316001248

Experimental method

X-RAY DIFFRACTION (2.2 Å)