UNC119 is required for G protein trafficking in sensory neurons

  • Nat Neurosci. 2011 Jun 5;14(7):874-80. doi: 10.1038/nn.2835.
Houbin Zhang  1 ,  Ryan Constantine ,  Sergey Vorobiev ,  Yang Chen ,  Jayaraman Seetharaman ,  Yuanpeng Janet Huang ,  Rong Xiao ,  Gaetano T Montelione ,  Cecilia D Gerstner ,  M Wayne Davis ,  George Inana ,  Frank G Whitby ,  Erik M Jorgensen ,  Christopher P Hill ,  Liang Tong ,  Wolfgang Baehr
Affiliations
  • 1. Department of Ophthalmology, University of Utah Health Science Center, Salt Lake City, Utah, USA.
PMID: 21642972 DOI: 10.1038/nn.2835
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.