Abstract
UNC119 is widely expressed among vertebrates and other phyla. We found that UNC119 recognized the acylated N terminus of the rod photoreceptor transducin α (Tα) subunit and Caenorhabditis elegans G proteins ODR-3 and GPA-13. The crystal structure of human UNC119 at 1.95-Å resolution revealed an immunoglobulin-like β-sandwich fold. Pulldowns and isothermal titration calorimetry revealed a tight interaction between UNC119 and acylated Gα peptides. The structure of co-crystals of UNC119 with an acylated Tα N-terminal peptide at 2.0 Å revealed that the lipid chain is buried deeply into UNC119's hydrophobic cavity. UNC119 bound Tα-GTP, inhibiting its GTPase activity, thereby providing a stable UNC119-Tα-GTP complex capable of diffusing from the inner segment back to the outer segment after light-induced translocation. UNC119 deletion in both mouse and C. elegans led to G protein mislocalization. Thus, UNC119 is a Gα subunit cofactor essential for G protein trafficking in sensory cilia.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / chemistry
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Adaptor Proteins, Signal Transducing / genetics
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Adaptor Proteins, Signal Transducing / metabolism*
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Animals
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Animals, Genetically Modified
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Caenorhabditis elegans
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Caenorhabditis elegans Proteins / genetics
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Cattle
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Dark Adaptation / genetics
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GTP Phosphohydrolases / metabolism
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GTP-Binding Protein alpha Subunits / deficiency
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GTP-Binding Protein alpha Subunits / metabolism*
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GTP-Binding Protein alpha Subunits, G12-G13 / genetics
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GTP-Binding Protein alpha Subunits, G12-G13 / metabolism
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GTP-Binding Protein alpha Subunits, Gi-Go
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Gene Expression Regulation / genetics
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Gene Expression Regulation / physiology*
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Glycine / genetics
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Green Fluorescent Proteins / genetics
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Humans
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Mice
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Mice, Knockout
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Models, Chemical
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Models, Molecular
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Mutation / genetics
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Protein Binding / genetics
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Protein Structure, Quaternary / genetics
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Protein Transport / genetics
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Sensory Receptor Cells / metabolism*
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Signal Transduction / genetics
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Time Factors
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Transducin / deficiency
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Transducin / genetics
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Transducin / metabolism*
Substances
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Adaptor Proteins, Signal Transducing
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Caenorhabditis elegans Proteins
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GTP-Binding Protein alpha Subunits
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Gnat1 protein, mouse
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UNC119 protein, human
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odr-3 protein, C elegans
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Green Fluorescent Proteins
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GTP Phosphohydrolases
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GTP-Binding Protein alpha Subunits, G12-G13
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GTP-Binding Protein alpha Subunits, Gi-Go
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Transducin
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Glycine