RETRACTED: Structure of the Parathyroid Hormone Receptor C Terminus Bound to the G-Protein Dimer Gβ1γ2

Christopher A. Johnston, Adam J. Kimple, Patrick M. Giguère, David P. Siderovski
2008 Structure  
A critical role of the Gbg dimer in heterotrimeric G-protein signaling is to facilitate the engagement and activation of the Ga subunit by cell-surface Gprotein-coupled receptors. However, high-resolution structural information of the connectivity between receptor and the Gbg dimer has not previously been available. Here, we describe the structural determinants of Gb 1 g 2 in complex with a C-terminal region of the parathyroid hormone receptor-1 (PTH1R) as obtained by X-ray crystallography. The
more » ... structure reveals that several critical residues within PTH1R contact only Gb residues located within the outer edge of WD1-and WD7-repeat segments of the Gb toroid structure. These regions encompass a predicted membrane-facing region of Gb thought to be oriented in a fashion that is accessible to the membrane-spanning receptor. Mutation of key receptor contact residues on Gb 1 leads to a selective loss of function in receptor/heterotrimer coupling while preserving Gb 1 g 2 activation of the effector phospholipase-C b.
doi:10.1016/j.str.2008.04.010 pmid:18611381 pmcid:PMC2601695 fatcat:g7ki6db6jjgd5oaoqzybf2p6dy