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
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis Regulatory Proteins / chemistry*
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Apoptosis Regulatory Proteins / genetics
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Armadillo Domain Proteins / chemistry
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Armadillo Domain Proteins / genetics
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Cell Cycle Proteins / chemistry*
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Cell Cycle Proteins / genetics
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DNA Repair Enzymes / chemistry*
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DNA Repair Enzymes / genetics
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Humans
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Intracellular Signaling Peptides and Proteins
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Membrane Glycoproteins / chemistry*
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Membrane Glycoproteins / genetics
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Nuclear Proteins / chemistry*
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Nuclear Proteins / genetics
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Protein Binding / genetics
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Protein Multimerization / genetics
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RNA Precursors / chemistry
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RNA Precursors / genetics
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RNA Splicing / genetics
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RNA Splicing Factors
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RNA-Binding Proteins / chemistry*
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RNA-Binding Proteins / genetics
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Tandem Repeat Sequences
Substances
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ADRM1 protein, human
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Apoptosis Regulatory Proteins
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Armadillo Domain Proteins
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CDC5L protein, human
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CTNNBL1 protein, human
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Cell Cycle Proteins
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Intracellular Signaling Peptides and Proteins
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Membrane Glycoproteins
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Nuclear Proteins
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RNA Precursors
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RNA Splicing Factors
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RNA-Binding Proteins
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DNA Repair Enzymes
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PRPF19 protein, human