Abstract
The crystal structure of the DNA complex of a STAT-1 homodimer has been determined at 2.9 A resolution. STAT-1 utilizes a DNA-binding domain with an immunoglobulin fold, similar to that of NFkappaB and the p53 tumor suppressor protein. The STAT-1 dimer forms a contiguous C-shaped clamp around DNA that is stabilized by reciprocal and highly specific interactions between the SH2 domain of one monomer and the C-terminal segment, phosphorylated on tyrosine, of the other. The phosphotyrosine-binding site of the SH2 domain in each monomer is coupled structurally to the DNA-binding domain, suggesting a potential role for the SH2-phosphotyrosine interaction in the stabilization of DNA interacting elements.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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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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Crystallography
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DNA / chemistry*
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DNA-Binding Proteins / chemistry*
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DNA-Binding Proteins / genetics
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Dimerization
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Humans
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Models, Molecular
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Molecular Conformation
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Molecular Sequence Data
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NF-kappa B / chemistry
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Oligodeoxyribonucleotides / chemistry*
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Peptide Fragments / chemistry
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Peptide Fragments / genetics
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Phosphorylation
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Phosphotyrosine / chemistry
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Protein Binding
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Protein Structure, Tertiary
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Recombinant Proteins / chemistry
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STAT1 Transcription Factor
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Sequence Homology, Amino Acid
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Synchrotrons
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Trans-Activators / chemistry*
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Trans-Activators / genetics
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Tumor Suppressor Protein p53 / chemistry
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src Homology Domains
Substances
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DNA-Binding Proteins
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NF-kappa B
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Oligodeoxyribonucleotides
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Peptide Fragments
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Recombinant Proteins
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STAT1 Transcription Factor
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STAT1 protein, human
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Trans-Activators
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Tumor Suppressor Protein p53
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Phosphotyrosine
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DNA