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

Yang Gao, Gözde Eskici, Sekar Ramachandran, Frédéric Poitevin, Alpay Burak Seven, Ouliana Panova, Georgios Skiniotis, Richard A Cerione

Molecular cell 2020 Oct 15

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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. Copyright © 2020 Elsevier Inc. All rights reserved.

Citation

Yang Gao, Gözde Eskici, Sekar Ramachandran, Frédéric Poitevin, Alpay Burak Seven, Ouliana Panova, Georgios Skiniotis, Richard A Cerione. Structure of the Visual Signaling Complex between Transducin and Phosphodiesterase 6. Molecular cell. 2020 Oct 15;80(2):237-245.e4