Structural Basis for the Functional Coupling of the Alternative Splicing Factors Smu1 and RED

Structure. 2016 May 3;24(5):762-773. doi: 10.1016/j.str.2016.03.016. Epub 2016 Apr 14.


The proteins Smu1 and RED have been jointly implicated in the regulation of alternative splicing, mitosis, and influenza virus infection, but how they interact and whether their diverse cellular functions are coupled is unknown. We identified an N-terminal region of Smu1 and a central region of RED that stably interact. Structural analyses revealed that the RED-binding region of Smu1 contains an N-terminal LisH motif linked to a core domain and a C-terminal α helix that folds back onto the LisH motif. Smu1 dimerizes via its LisH motif and C-terminal α helix and undergoes global conformational changes upon RED binding. In the ensuing hetero-tetrameric Smu1-RED complex, two molecules of RED use short α helices to bind hydrophobic grooves of two Smu1 core domains. Our results show how Smu1 and RED form a functional module that exhibits intriguing similarities to transcriptional co-repressor complexes, arranging multiple additional protein-protein interaction sites for contacting splicing and/or chromatin factors.

Keywords: B complex-specific proteins; LisH motif; X-ray crystallography; folding-upon-binding; pre-mRNA splicing; protein-protein interactions.

MeSH terms

  • Animals
  • Binding Sites
  • Caenorhabditis elegans / chemistry
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / chemistry*
  • Caenorhabditis elegans Proteins / metabolism
  • Intracellular Signaling Peptides and Proteins
  • Molecular Docking Simulation
  • Nuclear Proteins / chemistry*
  • Nuclear Proteins / metabolism
  • Protein Binding
  • Protein Multimerization


  • Caenorhabditis elegans Proteins
  • Intracellular Signaling Peptides and Proteins
  • Nuclear Proteins
  • SMU-2 protein, C elegans
  • Smu-1 protein, C elegans