3RBQ

Co-crystal structure of human UNC119 (retina gene 4) and an N-terminal Transducin-alpha mimicking peptide

Summary for 3RBQ

• Entry DOI: 10.2210/pdb3rbq/pdb
• Related: 3GQQ
• Descriptor: Protein unc-119 homolog A, Guanine nucleotide-binding protein G(t) subunit alpha-1 (3 entities in total)
• Functional Keywords: unc(uncoordinated)119 homolog c. elegans, g protein trafficking, acyl binnding protein, light-induced translocation, unc119 deletion, protein transport-lipid binding protein complex, protein transport/lipid binding protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 12
• Total formula weight: 145196.50

Authors

Constantine, R.,Whitby, F.G.,Hill, C.P.,Baehr, W. (deposition date: 2011-03-29, release date: 2011-06-08, Last modification date: 2023-09-13)

Primary citation

Zhang, H.,Constantine, R.,Vorobiev, S.,Chen, Y.,Seetharaman, J.,Huang, Y.J.,Xiao, R.,Montelione, G.T.,Gerstner, C.D.,Davis, M.W.,Inana, G.,Whitby, F.G.,Jorgensen, E.M.,Hill, C.P.,Tong, L.,Baehr, W.
UNC119 is required for G protein trafficking in sensory neurons.
Nat.Neurosci., 14:874-880, 2011

PubMed 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.

PubMed: 21642972
DOI: 10.1038/nn.2835

Experimental method

X-RAY DIFFRACTION (2 Å)