Abstract
CTNNBL1 is a spliceosome-associated protein that binds nuclear localization signals (NLSs) in splice factors CDC5L and Prp31 as well as the antibody diversifying enzyme AID. Here, crystal structures of human CTNNBL1 reveal a distinct structure from its closest homologue karyopherin-α. CTNNBL1 comprises a HEAT-like domain (including a nuclear export signal), a central armadillo domain, and a coiled-coil C-terminal domain. Structure-guided mutations of the region homologous to the karyopherin-α NLS-binding site fail to disrupt CTNNBL1-NLS interactions. Our results identify CTNNBL1 as a unique selective NLS-binding protein with striking differences from karyopherin-αs.
Keywords:
Armadillo domain; Nuclear import; Splicing.
Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Apoptosis Regulatory Proteins / chemistry*
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Apoptosis Regulatory Proteins / genetics
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Apoptosis Regulatory Proteins / metabolism
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Armadillo Domain Proteins / chemistry
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Armadillo Domain Proteins / genetics
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Armadillo Domain Proteins / metabolism
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Binding Sites / genetics
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Crystallography, X-Ray
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DNA Mutational Analysis
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Electrophoresis, Polyacrylamide Gel
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HEK293 Cells
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Humans
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Models, Molecular
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Molecular Sequence Data
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Mutation
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Nuclear Localization Signals / chemistry*
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Nuclear Localization Signals / metabolism
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Nuclear Proteins / chemistry*
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism
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Protein Binding
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Protein Structure, Secondary
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Protein Structure, Tertiary
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Sequence Homology, Amino Acid
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alpha Karyopherins / chemistry*
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alpha Karyopherins / genetics
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alpha Karyopherins / metabolism
Substances
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Apoptosis Regulatory Proteins
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Armadillo Domain Proteins
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CTNNBL1 protein, human
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Nuclear Localization Signals
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Nuclear Proteins
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alpha Karyopherins