Abstract
The sterol regulatory element-binding protein 2 (SREBP-2), a nuclear transcription factor that is essential for cholesterol metabolism, enters the nucleus through a direct interaction of its helix-loop-helix leucine zipper domain with importin-beta. We show the crystal structure of importin-beta complexed with the active form of SREBP-2. Importin-beta uses characteristic long helices like a pair of chopsticks to interact with an SREBP-2 dimer. Importin-beta changes its conformation to reveal a pseudo-twofold symmetry on its surface structure so that it can accommodate a symmetric dimer molecule. Importin-beta may use a similar strategy to recognize other dimeric cargoes.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Active Transport, Cell Nucleus*
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Amino Acid Motifs
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Amino Acid Sequence
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Animals
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Binding Sites
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Cell Nucleus / metabolism
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Crystallography, X-Ray
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DNA-Binding Proteins / chemistry*
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DNA-Binding Proteins / metabolism*
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Dimerization
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Helix-Loop-Helix Motifs
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Humans
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Hydrophobic and Hydrophilic Interactions
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Mice
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Models, Molecular
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Molecular Sequence Data
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Nuclear Localization Signals
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Nuclear Pore / metabolism
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Protein Binding
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Protein Conformation*
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Protein Structure, Secondary
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Protein Structure, Tertiary
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Sterol Regulatory Element Binding Protein 2
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Transcription Factors / chemistry*
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Transcription Factors / metabolism*
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beta Karyopherins / chemistry*
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beta Karyopherins / metabolism*
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ran GTP-Binding Protein / metabolism
Substances
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DNA-Binding Proteins
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Nuclear Localization Signals
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SREBF2 protein, human
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Srebf2 protein, mouse
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Sterol Regulatory Element Binding Protein 2
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Transcription Factors
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beta Karyopherins
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ran GTP-Binding Protein