7jsn

Publication Abstract from PubMed

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 alpha subunit (GalphaT.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 GalphaT. The structure reveals two GalphaT.GTP subunits engaging the PDE6 hetero-tetramer at both the PDE6 catalytic core and the PDEgamma 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 GalphaT.GTP subunits and PDE6 that supports an alternating-site catalytic mechanism.

Structure of the Visual Signaling Complex between Transducin and Phosphodiesterase 6.,Gao Y, Eskici G, Ramachandran S, Poitevin F, Seven AB, Panova O, Skiniotis G, Cerione RA Mol Cell. 2020 Oct 15;80(2):237-245.e4. doi: 10.1016/j.molcel.2020.09.013. Epub, 2020 Oct 1. PMID:33007200^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.