Dataset Information

The solution structure of the transducin-?-uncoordinated 119 protein complex suggests occlusion of the G????-binding sites.

ABSTRACT: Uncoordinated 119 protein (UNC119) is a partner of transducin-? subunit (G?t ) that is essential for transducin trafficking in rod photoreceptors. The interaction is known to involve binding of the acylated N terminus of G?t 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 G?t (G?t *) and UNC119??????, and examined the solution structure by small angle X-ray scattering and chemical crosslinking. The solution structure of the G?t -UNC119?????? complex was derived with rigid body/ab initio modeling against the small angle X-ray scattering data by use of known atomic structures of G?t and UNC119, and a distance constraint based on the protein crosslinking with p-phenyldimaleimide. The model of the G?t -UNC119?????? complex indicates rotation and bending of the N-terminal ?-helix of G?t from its position in the structure of the heterotrimeric G-protein transducin (Gt ). This allows a considerably more compact complex conformation, which also suggests a novel interface involving the switch II/?3-?5 surface of G?t . Supporting a novel interface, UNC119 was found to bind full-length G?t * more strongly than the G?t N-terminal peptide. Furthermore, UNC119 competed with the effector molecule phosphodiesterase-6 ?-subunit, which is known to bind to the same surface of G?t . The solution structure of the G?t -UNC119 complex suggests that the ability of UNC119 to dissociate Gt subunits and release G?t from the membrane is attributable to disruption and sterical occlusion of the G????-binding sites on G?t .

SUBMITTER: Cheguru P

PROVIDER: S-EPMC4310827 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The solution structure of the transducin-α-uncoordinated 119 protein complex suggests occlusion of the Gβ₁γ₁-binding sites.

Cheguru Pallavi P Majumder Anurima A Yadav Ravi R Gopalakrishna Kota N KN Gakhar Lokesh L Artemyev Nikolai O NO

The FEBS journal 20141212 3

Uncoordinated 119 protein (UNC119) is a partner of transducin-α subunit (Gαt ) that is 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 (Gαt *) and UNC119₅₀₋₂₄₀, and examined the solution structure by small angle X-ray scattering and ...[more]

PMID: 25425538

Similar Datasets

Project description:Bovine leukemia virus (BLV) is a deltaretrovirus that infects domestic cattle. The structural protein Gag, found in all retroviruses, is a polyprotein comprising three major functional domains: matrix (MA), capsid (CA), and nucleocapsid (NC). Previous studies have shown that both mature BLV MA and NC are able to bind to nucleic acids; however, the viral assembly process and packaging of viral genomic RNA requires full-length Gag to produce infectious particles. Compared to lentiviruses, little is known about the structure of the Gag polyprotein of deltaretroviruses. In this work, structural models of full-length BLV Gag and Gag lacking the MA domain were generated based on previous structural data of individual domains, homology modeling, and flexible fitting to SAXS data using molecular dynamics. The models were used in molecular dynamic simulations to determine the relative mobility of the protein backbone. Functional annealing assays revealed the role of MA in the nucleic acid chaperone activity of BLV Gag. Our results show that full-length BLV Gag has an elongated rod-shaped structure that is relatively rigid, with the exception of the linker between the MA and CA domains. Deletion of the MA domain maintains the elongated structure but alters the rate of BLV Gag-facilitated annealing of two complementary nucleic acids. These data are consistent with a role for the MA domain of retroviral Gag proteins in modulating nucleic acid binding and chaperone activity. IMPORTANCE: BLV is a retrovirus that is found worldwide in domestic cattle. Since BLV infection has serious implications for agriculture, and given its similarities to human retroviruses such as HTLV-1, the development of an effective treatment would have numerous benefits. The Gag polyprotein exists in all retroviruses and is a key player in viral assembly. However, the full-length structure of Gag from any virus has yet to be elucidated at high resolution. This study provides structural data for BLV Gag and could be a starting point for modeling Gag-small molecule interactions with the ultimate goal of developing of a new class of pharmaceuticals.

Dataset Information

The solution structure of the transducin-?-uncoordinated 119 protein complex suggests occlusion of the G????-binding sites.

Publications

The solution structure of the transducin-α-uncoordinated 119 protein complex suggests occlusion of the Gβ₁γ₁-binding sites.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets