Abstract
G protein-coupled receptor kinase 2 (GRK2) plays a key role in the desensitization of G protein-coupled receptor signaling by phosphorylating activated heptahelical receptors and by sequestering heterotrimeric G proteins. We report the atomic structure of GRK2 in complex with Galphaq and Gbetagamma, in which the activated Galpha subunit of Gq is fully dissociated from Gbetagamma and dramatically reoriented from its position in the inactive Galphabetagamma heterotrimer. Galphaq forms an effector-like interaction with the GRK2 regulator of G protein signaling (RGS) homology domain that is distinct from and does not overlap with that used to bind RGS proteins such as RGS4.
Publication types
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Research Support, N.I.H., Extramural
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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.
MeSH terms
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Amino Acid Sequence
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Amino Acid Substitution
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Animals
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Cattle
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Crystallography, X-Ray
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GTP-Binding Protein alpha Subunits, Gq-G11 / chemistry*
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GTP-Binding Protein alpha Subunits, Gq-G11 / metabolism
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GTP-Binding Protein beta Subunits / chemistry*
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GTP-Binding Protein beta Subunits / metabolism
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GTP-Binding Protein gamma Subunits / chemistry*
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GTP-Binding Protein gamma Subunits / metabolism
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Hydrogen Bonding
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Models, Molecular
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Molecular Sequence Data
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Mutation
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Protein Binding
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Protein Conformation
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Protein Structure, Secondary
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Protein Structure, Tertiary
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Protein Subunits / chemistry
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RGS Proteins / metabolism
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Signal Transduction
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beta-Adrenergic Receptor Kinases / chemistry*
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beta-Adrenergic Receptor Kinases / metabolism
Substances
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G-protein Beta gamma
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GTP-Binding Protein beta Subunits
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GTP-Binding Protein gamma Subunits
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Protein Subunits
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RGS Proteins
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beta-Adrenergic Receptor Kinases
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GTP-Binding Protein alpha Subunits, Gq-G11