|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 genetics physiology deficiency |
|Humans Animals Models, Molecular Protein Binding Models, Chemical Protein Structure, Quaternary Signal Transduction Mutation Time Factors Mice GTP Phosphohydrolases Cattle Adaptor Proteins, Signal Transducing Green Fluorescent Proteins Animals, Genetically Modified Caenorhabditis elegans Gene Expression Regulation Protein Transport Caenorhabditis elegans Proteins Glycine Transducin Dark Adaptation GTP-Binding Protein alpha Subunits GTP-Binding Protein alpha Subunits, G12-G13 GTP-Binding Protein alpha Subunits, Gi-Go Mice, Knockout Sensory Receptor Cells |
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