Abstract
Spt6 is an essential transcription elongation factor and histone chaperone that binds the C-terminal repeat domain (CTD) of RNA polymerase II. We show here that Spt6 contains a tandem SH2 domain with a novel structure and CTD-binding mode. The tandem SH2 domain binds to a serine 2-phosphorylated CTD peptide in vitro, whereas its N-terminal SH2 subdomain, which we previously characterized, does not. CTD binding requires a positively charged crevice in the C-terminal SH2 subdomain, which lacks the canonical phospho-binding pocket of SH2 domains and had previously escaped detection. The tandem SH2 domain is apparently required for transcription elongation in vivo as its deletion in cells is lethal in the presence of 6-azauracil.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Chromatin / chemistry
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Crystallography, X-Ray / methods
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Histone Chaperones
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Humans
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Molecular Sequence Data
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Nuclear Proteins / chemistry
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Nuclear Proteins / physiology*
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Peptides / chemistry
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Phosphorylation
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Protein Structure, Tertiary
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RNA Polymerase II / chemistry
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Saccharomyces cerevisiae / metabolism*
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Saccharomyces cerevisiae Proteins / chemistry
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Saccharomyces cerevisiae Proteins / physiology*
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Sequence Homology, Amino Acid
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Transcription, Genetic
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Transcriptional Elongation Factors / chemistry
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Transcriptional Elongation Factors / physiology*
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src Homology Domains
Substances
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Chromatin
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Histone Chaperones
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Nuclear Proteins
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Peptides
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SPT6 protein, S cerevisiae
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Saccharomyces cerevisiae Proteins
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Transcriptional Elongation Factors
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RNA Polymerase II