Abstract
HIP1 crystal structures solved in our laboratory revealed abnormalities in the coiled-coil region, suggesting intrinsic plasticity. To test this, specific amino acids in the coiled-coil were mutated. The apparent thermal stability of HIP1 was altered when Thr528 and Glu531 were replaced by leucine, and was enhanced when Lys510 was also mutated. In cells, HIP1 mutant expression produced aggregation. MTS and flow cytometry indicate a correlation between aggregated HIP1 and enhanced cell death. These data support the idea that flexibility of the HIP1 coiled-coil domain is important for normal function and may lead to new insights into Huntington's disease.
Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Amino Acid Substitution
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Base Sequence
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Cell Death / genetics
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Cell Death / physiology
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DNA Primers / genetics
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DNA-Binding Proteins / chemistry*
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / physiology*
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HEK293 Cells
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Humans
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Huntingtin Protein
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Huntington Disease / genetics
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Huntington Disease / pathology
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Huntington Disease / physiopathology
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Models, Molecular
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Mutagenesis, Site-Directed
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Mutant Proteins / chemistry
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Mutant Proteins / genetics
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Mutant Proteins / physiology
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Nerve Tissue Proteins / chemistry
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / physiology
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Protein Multimerization
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Protein Stability
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Protein Structure, Tertiary
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Recombinant Proteins / chemistry
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Transfection
Substances
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DNA Primers
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DNA-Binding Proteins
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HIP1 protein, human
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HTT protein, human
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Huntingtin Protein
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Mutant Proteins
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Nerve Tissue Proteins
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Recombinant Proteins