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Structure of the Visual Signaling Complex between Transducin and Phosphodiesterase 6.

Abstract：

:Heterotrimeric G proteins communicate signals from activated G protein-coupled receptors to downstream effector proteins. In the phototransduction pathway responsible for vertebrate vision, the G protein-effector complex is composed of the GTP-bound transducin α subunit (GαT·GTP) and the cyclic GMP (cGMP) phosphodiesterase 6 (PDE6), which stimulates cGMP hydrolysis, leading to hyperpolarization of the photoreceptor cell. Here we report a cryo-electron microscopy (cryoEM) structure of PDE6 complexed to GTP-bound GαT. The structure reveals two GαT·GTP subunits engaging the PDE6 hetero-tetramer at both the PDE6 catalytic core and the PDEγ subunits, driving extensive rearrangements to relieve all inhibitory constraints on enzyme catalysis. Analysis of the conformational ensemble in the cryoEM data highlights the dynamic nature of the contacts between the two GαT·GTP subunits and PDE6 that supports an alternating-site catalytic mechanism.

journal_name

Mol Cell

journal_title

Molecular cell

authors

Gao Y,Eskici G,Ramachandran S,Poitevin F,Seven AB,Panova O,Skiniotis G,Cerione RA

doi

10.1016/j.molcel.2020.09.013

subject

Has Abstract

pub_date

2020-10-15 00:00:00

pages

237-245.e4

issue

2

eissn

1097-2765

issn

1097-4164

pii

S1097-2765(20)30621-3

journal_volume

80

pub_type

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