Abstract
Overexpression of multiple copies in T-cell lymphoma-1 (MCT-1) oncogene accompanies malignant phenotypic changes in human lymphoma cells. Specific disruption of MCT-1 results in reduced tumorigenesis, suggesting a potential for MCT-1-targeted therapeutic strategy. MCT-1 is known as a cap-binding protein and has a putative RNA-binding motif, the PUA-domain, at its C-terminus. We determined the crystal structure of apo MCT-1 at 1.7 Å resolution using the surface entropy reduction method. Notwithstanding limited sequence identity to its homologs, the C-terminus of MCT-1 adopted a typical PUA-domain fold that includes secondary structural elements essential for RNA recognition. The surface of the N-terminal domain contained positively charged patches that are predicted to contribute to RNA-binding.
Copyright © 2012 Wiley Periodicals, Inc.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alanine / chemistry
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Alanine / genetics
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Amino Acid Motifs
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Amino Acid Sequence
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Biophysical Phenomena
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Cell Cycle Proteins / chemistry*
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Cell Cycle Proteins / genetics
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Chromatography, Gel
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Circular Dichroism
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Cloning, Molecular
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Crystallography / methods
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DNA, Complementary / chemistry
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DNA, Complementary / genetics
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Entropy
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Escherichia coli / chemistry
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Escherichia coli / genetics
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Genetic Vectors / chemistry
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Genetic Vectors / genetics
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Humans
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Molecular Sequence Data
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Molecular Weight
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Mutation*
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Oncogene Proteins / chemistry*
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Oncogene Proteins / genetics
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Protein Folding
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Protein Structure, Secondary
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RNA-Binding Proteins / chemistry
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Recombinant Fusion Proteins / chemistry*
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Recombinant Fusion Proteins / genetics
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Sequence Homology, Nucleic Acid
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Static Electricity
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Temperature
Substances
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Cell Cycle Proteins
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DNA, Complementary
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MCTS1 protein, human
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Oncogene Proteins
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RNA-Binding Proteins
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Recombinant Fusion Proteins
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Alanine