Skip to Content
The Solution Structure of the Transducin-α/UNC119 Complex suggests occlusion of the Gβ1γ1-binding sites.
FEBS J. 2014 Nov 25;
Authors: Cheguru P, Majumder A, Yadav R, Gopalakrishna KN, Gakhar L, Artemyev NO
Uncoordinated 119 protein (UNC119) is a partner of transducin-α (Gαt ) essential for transducin trafficking in rod photoreceptors. The interaction is known to involve binding of the acylated N-terminus of Gαt to the hydrophobic pocket of UNC119. To gain insights into the mechanism of transducin trafficking, we isolated a highly pure protein complex between myristoylated chimeric Gαt *-subunit and UNC11950-240 and examined the solution structure by Small Angle X-ray Scattering (SAXS) and chemical crosslinking. The solution structure of the Gαt -UNC11950-240 complex was derived with rigid-body/ab initio modeling against the SAXS data using known atomic structures of Gαt and UNC119 and a distance constraint based on the protein crosslinking with para-phenyldimaleimide. The model of the Gαt -UNC11950-240 complex indicates rotation and bending of the N-terminal α-helix of Gαt from its position in the structure of heterotrimeric Gt . This allows a considerably more compact complex conformation, which also suggests a novel interface involving the switch II/α3-β5 surface of Gαt . Supporting a novel interface, UNC119 was found to bind stronger the full-length Gαt * compared to the Gαt N-terminal peptide. Furthermore, UNC119 competed with the effector molecule, PDE6 γ-subunit, known to bind the same surface of Gαt . The solution structure of the Gαt -UNC119 complex suggests that the ability of UNC119 to dissociate Gt subunits and release Gαt from the membrane is due to disruption and sterical occlusion of the Gβ1 γ1 -binding sites on Gαt . This article is protected by copyright. All rights reserved.
PMID: 25425538 [PubMed - as supplied by publisher]