title: UNC119 is required for G protein trafficking in sensory neurons.
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.
authors.affiliation: Department of Ophthalmology, University of Utah Health Science Center, Salt Lake City, Utah, USA.
authors.forename: Houbin
authors.initials: H
authors.lastname: Zhang
authors.forename: Ryan
authors.initials: R
authors.lastname: Constantine
authors.forename: Sergey
authors.initials: S
authors.lastname: Vorobiev
authors.forename: Yang
authors.initials: Y
authors.lastname: Chen
authors.forename: Jayaraman
authors.initials: J
authors.lastname: Seetharaman
authors.forename: Yuanpeng Janet
authors.initials: YJ
authors.lastname: Huang
authors.forename: Rong
authors.initials: R
authors.lastname: Xiao
authors.forename: Gaetano T
authors.initials: GT
authors.lastname: Montelione
authors.forename: Cecilia D
authors.initials: CD
authors.lastname: Gerstner
authors.forename: M Wayne
authors.initials: MW
authors.lastname: Davis
authors.forename: George
authors.initials: G
authors.lastname: Inana
authors.forename: Frank G
authors.initials: FG
authors.lastname: Whitby
authors.forename: Erik M
authors.initials: EM
authors.lastname: Jorgensen
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Hill
authors.forename: Liang
authors.initials: L
authors.lastname: Tong
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Baehr
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics; D002417:Cattle; D003623:Dark Adaptation / Q000235:genetics; D020558:GTP Phosphohydrolases / Q000378:metabolism; D044385:GTP-Binding Protein alpha Subunits / Q000172:deficiency / Q000378:metabolism*; D044365:GTP-Binding Protein alpha Subunits, G12-G13 / Q000235:genetics / Q000378:metabolism; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology*; D005998:Glycine / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008956:Models, Chemical; D008958:Models, Molecular; D009154:Mutation / Q000235:genetics; D011485:Protein Binding / Q000235:genetics; D020836:Protein Structure, Quaternary / Q000235:genetics; D021381:Protein Transport / Q000235:genetics; D011984:Sensory Receptor Cells / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D013997:Time Factors; D015293:Transducin / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D029742:Caenorhabditis elegans Proteins; D044385:GTP-Binding Protein alpha Subunits; C488949:Gnat1 protein, mouse; C098032:UNC119 protein, human; C110666:odr-3 protein, C elegans; D049452:Green Fluorescent Proteins; D020558:GTP Phosphohydrolases; D044365:GTP-Binding Protein alpha Subunits, G12-G13; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D015293:Transducin; D005998:Glycine