Abstract
Guanine nucleotide exchange factors for the Rho family of GTPases contain a Dbl homology (DH) domain responsible for catalysis and a pleckstrin homology (PH) domain whose function is unknown. Here we describe the solution structure of the N-terminal DH domain of Trio that catalyzes nucleotide exchange for Rac1. The all-alpha-helical protein has a very different structure compared to other exchange factors. Based on site-directed mutagenesis, functionally important residues of the DH domain were identified. They are all highly conserved and reside in close proximity on two a helices. In addition, we have discovered a unique capability of the PH domain to enhance nucleotide exchange in DH domain-containing proteins.
MeSH terms
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Blood Proteins / chemistry
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Blood Proteins / genetics
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Guanine Nucleotide Exchange Factors*
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Magnetic Resonance Spectroscopy
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Molecular Sequence Data
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Mutagenesis
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Nucleotides / metabolism*
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Phosphoproteins / chemistry*
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Phosphoproteins / genetics*
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Phosphoproteins / metabolism
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Protein Serine-Threonine Kinases / chemistry*
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Protein Serine-Threonine Kinases / genetics*
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Protein Serine-Threonine Kinases / metabolism
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Protein Structure, Secondary
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Protein Structure, Tertiary
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Proto-Oncogene Proteins / genetics*
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Sequence Homology, Amino Acid
Substances
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Blood Proteins
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Guanine Nucleotide Exchange Factors
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Nucleotides
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Phosphoproteins
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Proto-Oncogene Proteins
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platelet protein P47
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Protein Serine-Threonine Kinases
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TRIO protein, human