|Nature neuroscience (2011) 14:874-80|
|Northeast Structural Genomics Consortium|
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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.
|metabolism chemistry physiology deficiency genetics |
|Dark Adaptation Signal Transduction GTP-Binding Protein alpha Subunits, Gi-Go Adaptor Proteins, Signal Transducing Caenorhabditis elegans Mice, Knockout Transducin Models, Chemical GTP-Binding Protein alpha Subunits, G12-G13 Glycine Mice Green Fluorescent Proteins Models, Molecular Mutation Protein Structure, Quaternary Protein Transport Humans Time Factors Caenorhabditis elegans Proteins Animals Sensory Receptor Cells Cattle Animals, Genetically Modified Protein Binding Gene Expression Regulation GTP Phosphohydrolases GTP-Binding Protein alpha Subunits |
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