Abstract
The interaction of the serine/threonine kinase Pelle and adaptor protein Tube through their N-terminal death domains leads to the nuclear translocation of the transcription factor Dorsal and activation of zygotic patterning genes during Drosophila embryogenesis. Crystal structure of the Pelle and Tube death domain heterodimer reveals that the two death domains adopt a six-helix bundle fold and are arranged in an open-ended linear array with plastic interfaces mediating their interactions. The Tube death domain has an insertion between helices 2 and 3, and a C-terminal tail making significant and indispensable contacts in the heterodimer. In vivo assays of Pelle and Tube mutants confirmed that the integrity of the major heterodimer interface is critical to the activity of these molecules.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Binding Sites
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Cell Death*
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Crystallization
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Crystallography
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Dimerization
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Drosophila Proteins*
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Insect Proteins / chemistry*
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Insect Proteins / metabolism
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Models, Molecular
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Molecular Sequence Data
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Mutagenesis, Site-Directed
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NF-kappa B / metabolism
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Nuclear Proteins / metabolism
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Peptide Fragments / chemistry
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Peptide Fragments / metabolism
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Phosphoproteins / metabolism
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Protein Binding
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Protein Serine-Threonine Kinases / chemistry*
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Protein Serine-Threonine Kinases / metabolism
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Protein Structure, Tertiary*
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Sequence Homology, Amino Acid
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Transcription Factors*
Substances
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Drosophila Proteins
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Insect Proteins
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NF-kappa B
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Nuclear Proteins
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Peptide Fragments
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Phosphoproteins
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Transcription Factors
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dl protein, Drosophila
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tub protein, Drosophila
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pll protein, Drosophila
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Protein Serine-Threonine Kinases