Abstract
The crystal structure of transducin's betagamma subunits complexed with phosducin, which regulates Gtbetagamma activity, has been solved to 2.4 angstroms resolution. Phosducin has two domains that wrap around Gtbetagamma to form an extensive interface. The N-terminal domain binds loops on the "top" Gtbeta surface, overlapping the Gtalpha binding surface, explaining how phosducin blocks Gtbetagamma's interaction with Gtalpha. The C-terminal domain shows structural homology to thioredoxin and binds the outer strands of Gtbeta's seventh and first blades in a manner likely to disrupt Gtbetagamma's normal orientation relative to the membrane and receptor. Phosducin's Ser-73, which when phosphorylated inhibits phosducin's function, points away from Gtbetagamma, toward a large flexible loop. Thus phosphorylation is not likely to affect the interface directly, but rather indirectly through an induced conformational change.
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, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animal Population Groups / metabolism
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Animals
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Cattle
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Crystallography, X-Ray
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DNA, Complementary / genetics
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Eye Proteins / chemistry*
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GTP-Binding Protein Regulators
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Humans
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Macromolecular Substances
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Mice
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Models, Molecular*
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Molecular Sequence Data
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Phosphoproteins / chemistry*
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Phosphorylation
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Protein Binding
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Protein Conformation*
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Protein Processing, Post-Translational
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Rats
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Recombinant Fusion Proteins / chemistry
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Rod Cell Outer Segment / chemistry
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Sequence Alignment
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Sequence Homology, Amino Acid
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Species Specificity
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Static Electricity
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Thioredoxins / chemistry
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Transducin / chemistry*
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Yeasts / metabolism
Substances
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DNA, Complementary
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Eye Proteins
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GTP-Binding Protein Regulators
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Macromolecular Substances
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Phosphoproteins
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Recombinant Fusion Proteins
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phosducin
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Thioredoxins
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Transducin
Associated data
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GENBANK/L15355
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GENBANK/Z46727
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SWISSPROT/P00274
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SWISSPROT/P19632
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SWISSPROT/P20942