Structural insights into the novel ARM-repeat protein CTNNBL1 and its association with the hPrp19-CDC5L complex

Acta Crystallogr D Biol Crystallogr. 2014 Mar;70(Pt 3):780-8. doi: 10.1107/S139900471303318X. Epub 2014 Feb 22.

Abstract

The hPrp19-CDC5L complex plays a crucial role during human pre-mRNA splicing by catalytic activation of the spliceosome. In order to elucidate the molecular architecture of the hPrp19-CDC5L complex, the crystal structure of CTNNBL1, one of the major components of this complex, was determined. Unlike canonical ARM-repeat proteins such as β-catenin and importin-α, CTNNBL1 was found to contain a twisted and extended ARM-repeat structure at the C-terminal domain and, more importantly, the protein formed a stable dimer. A highly negatively charged patch formed in the N-terminal ARM-repeat domain of CTNNBL1 provides a binding site for CDC5L, a binding partner of the protein in the hPrp19-CDC5L complex, and these two proteins form a complex with a stoichiometry of 2:2. These findings not only present the crystal structure of a novel ARM-repeat protein, CTNNBL1, but also provide insights into the detailed molecular architecture of the hPrp19-CDC5L complex.

Keywords: ARM-repeat proteins; CTNNBL1; hPrp19–CDC5L complex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis Regulatory Proteins / chemistry*
  • Apoptosis Regulatory Proteins / genetics
  • Armadillo Domain Proteins / chemistry
  • Armadillo Domain Proteins / genetics
  • Cell Cycle Proteins / chemistry*
  • Cell Cycle Proteins / genetics
  • DNA Repair Enzymes / chemistry*
  • DNA Repair Enzymes / genetics
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Membrane Glycoproteins / chemistry*
  • Membrane Glycoproteins / genetics
  • Nuclear Proteins / chemistry*
  • Nuclear Proteins / genetics
  • Protein Binding / genetics
  • Protein Multimerization / genetics
  • RNA Precursors / chemistry
  • RNA Precursors / genetics
  • RNA Splicing / genetics
  • RNA Splicing Factors
  • RNA-Binding Proteins / chemistry*
  • RNA-Binding Proteins / genetics
  • Tandem Repeat Sequences

Substances

  • ADRM1 protein, human
  • Apoptosis Regulatory Proteins
  • Armadillo Domain Proteins
  • CDC5L protein, human
  • CTNNBL1 protein, human
  • Cell Cycle Proteins
  • Intracellular Signaling Peptides and Proteins
  • Membrane Glycoproteins
  • Nuclear Proteins
  • RNA Precursors
  • RNA Splicing Factors
  • RNA-Binding Proteins
  • DNA Repair Enzymes
  • PRPF19 protein, human

Associated data

  • PDB/4MFU
  • PDB/4MFV