biostudies-literatureUnknown96(9)Kisselev OGPhotoactivation of the retinal photoreceptor rhodopsin proceeds through a cascade of intermediates, resulting in protein-protein interactions catalyzing the activation of the G-protein transducin (Gt). Using stabilization and photoregeneration of the receptor's signaling state and Gt activation assays, we provide evidence for a two-site sequential fit mechanism of Gt activation. We show that the C-terminal peptide from the Gt gamma-subunit, Gtgamma(50-71)farnesyl, can replace the holoprotein in stabilizing rhodopsin's active intermediate metarhodopsin II (MII). However, the peptide cannot replace the Gtbeta gamma complex in direct activation assays. Competition by Gtgamma(50-71)farnesyl with Gt for the active receptor suggests a pivotal role for Gtbeta gamma in signal transfer from MII to Proceedings of the National Academy of Sciences of the United States of America4898-903https://www.ebi.ac.uk/biostudies/studies/S-EPMC21788biostudies-literatureSignal transfer from rhodopsin to the G-protein: evidence for a two-site sequential fit mechanism.PMC21788Meyer CKKisselev OGHeck MErnst OPHofmann KPfalseSignal transfer from rhodopsin to the G-protein: evidence for a two-site sequential fit mechanism.Photoactivation of the retinal photoreceptor rhodopsin proceeds through a cascade of intermediates, resulting in protein-protein interactions catalyzing the activation of the G-protein transducin (Gt). Using stabilization and photoregeneration of the receptor's signaling state and Gt activation assays, we provide evidence for a two-site sequential fit mechanism of Gt activation. We show that the C-terminal peptide from the Gt gamma-subunit, Gtgamma(50-71)farnesyl, can replace the holoprotein in stabilizing rhodopsin's active intermediate metarhodopsin II (MII). However, the peptide cannot replace the Gtbeta gamma complex in direct activation assays. Competition by Gtgamma(50-71)farnesyl with Gt for the active receptor suggests a pivotal role for Gtbeta gamma in signal transfer from MII to 1999-01-01T00:00:00Z1999 Apr2025-05-29T19:44:14.631Z2019-03-27T00:17:48ZS-EPMC217881022039010.1073/pnas.96.9.4898