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Phosducin induces a structural change in transducin ??

Loew, Andreas, Ho, Yee-Kin, Blundell, Tom and Bax, Benjamin 1998. Phosducin induces a structural change in transducin ?? Structure 6 (8) , pp. 1007-1019. 10.1016/S0969-2126(98)00102-6

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Abstract

Background: Phosducin binds tightly to the βγ subunits (Gtβγ) of the heterotrimeric G protein transducin, preventing Gtβγ reassociation with Gtα–GDP and thereby inhibiting the G-protein cycle. Phosducin-like proteins appear to be widely distributed and may play important roles in regulating many heterotrimeric G-protein signaling pathways. Results: The 2.8 å crystal structure of a complex of bovine retinal phosducin with Gtβγ shows how the two domains of phosducin cover one side and the top of the seven-bladed β propeller of Gtβγ. The binding of phosducin induces a distinct structural change in the β propeller of Gtβγ, such that a small cavity opens up between blades 6 and 7. Electron density in this cavity has been assigned to the farnesyl moiety of the γ subunit. Conclusions:βγ subunits of heterotrimeric G proteins can exist in two distinct conformations. In the R (relaxed) state, corresponding to the structure of the free βγ or the structure of βγ in the αβγ heterotrimer, the hydrophobic farnesyl moiety of the γ subunit is exposed, thereby mediating membrane association. In the T (tense) state, as observed in the phosducin–Gtβγ structure, the farnesyl moiety of the γ subunit is effectively buried in the cavity formed between blades 6 and 7 of the β subunit. Binding of phosducin to Gtβγ induces the formation of this cavity, resulting in a switch from the R to the T conformation. This sequesters βγ from the membrane to the cytosol and turns off the signal-transduction cascade. Regulation of this membrane association/dissociation switch of Gtβγ by phosducin may be a general mechanism for attenuation of G protein coupled signal transduction cascades.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Publisher: Elsevier
ISSN: 0969-2126
Last Modified: 06 Jul 2018 11:05
URI: http://orca.cf.ac.uk/id/eprint/112639

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