RT Journal Article
SR Electronic
T1 Structure of the Visual Signaling Complex between Transducin and Phosphodiesterase 6
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.04.01.020651
DO 10.1101/2020.04.01.020651
A1 Yang Gao
A1 Gözde Eskici
A1 Sekar Ramachandran
A1 Frédéric Poitevin
A1 Alpay Burak Seven
A1 Ouliana Panova
A1 Georgios Skiniotis
A1 Richard A. Cerione
YR 2020
UL http://biorxiv.org/content/early/2020/04/03/2020.04.01.020651.abstract
AB 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 comprised of the GTP-bound transducin α subunit (GαT·GTP) and the cyclic GMP (cGMP) phosphodiesterase 6 (PDE6), which stimulates cGMP hydrolysis to transmit signals to the optic nerve. 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 support an alternating-site catalytic mechanism.