A novel protein-protein interaction in the RES (REtention and Splicing) complex.
Fiche publication
Date publication
octobre 2014
Journal
The Journal of biological chemistry
Auteurs
Membres identifiés du Cancéropôle Est :
Dr SERAPHIN Bertrand
Tous les auteurs :
Tripsianes K, Friberg A, Barrandon C, Brooks M, van Tilbeurgh H, Seraphin B, Sattler M
Lien Pubmed
Résumé
The retention and splicing (RES) complex is a conserved spliceosome-associated module that was shown to enhance splicing of a subset of transcripts and promote the nuclear retention of unspliced pre-mRNAs in yeast. The heterotrimeric RES complex is organized around the Snu17p protein that binds to both the Bud13p and Pml1p subunits. Snu17p exhibits an RRM domain that resembles a U2AF homology motif (UHM) and Bud13p harbors a Trp residue reminiscent of an UHM-ligand motif (ULM). It has therefore been proposed that the interaction between Snu17p and Bud13p resembles canonical UHM-ULM complexes. Here, we have used biochemical and NMR structural analysis to characterize the structure of the yeast Snu17p-Bud13p complex. Unlike known UHMs that sequester the Trp residue of the ULM ligand in a hydrophobic pocket, Snu17p and Bud13p utilize a large interaction surface formed around the two helices of the Snu17p domain. In total 18 residues of the Bud13p ligand wrap around the Snu17p helical surface in an U-turn-like arrangement. The invariant Trp(232) in Bud13p is located in the center of the turn, and contacts surface residues of Snu17p. The structural data are supported by mutational analysis and indicate that Snu17p provides an extended binding surface with Bud13p that is notably distinct from canonical UHM-ULM interactions. Our data highlight structural diversity in RRM-protein interactions, analogous to the one seen for nucleic acid interactions.
Mots clés
Amino Acid Sequence, Binding Sites, Carrier Proteins, chemistry, Escherichia coli, genetics, Gene Expression, Hydrophobic and Hydrophilic Interactions, Models, Molecular, Molecular Sequence Data, Phosphorylation, Protein Binding, Protein Interaction Domains and Motifs, Protein Structure, Secondary, RNA Precursors, biosynthesis, RNA Splicing, RNA, Fungal, biosynthesis, Recombinant Proteins, chemistry, Ribonucleoprotein, U2 Small Nuclear, chemistry, Saccharomyces cerevisiae, chemistry, Saccharomyces cerevisiae Proteins, chemistry, Sequence Alignment, Spliceosomes, chemistry, Tryptophan, chemistry
Référence
J. Biol. Chem.. 2014 Oct;289(41):28640-50