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

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


A critical role of the Gβγ dimer in heterotrimeric G-protein signaling is to facilitate the engagement and activation of the Gα subunit by cell-surface G-protein-coupled receptors. However, high-resolution structural information of the connectivity between receptor and the Gβγ dimer has not previously been available. Here, we describe the structural determinants of Gβ1γ2 in complex with a C-terminal region of the parathyroid hormone receptor-1 (PTH1R) as obtained by X-ray crystallography. The structure reveals that several critical residues within PTH1R contact only Gβ residues located within the outer edge of WD1- and WD7-repeat segments of the Gβ toroid structure. These regions encompass a predicted membrane-facing region of Gβ thought to be oriented in a fashion that is accessible to the membrane-spanning receptor. Mutation of key receptor contact residues on Gβ1 leads to a selective loss of function in receptor/heterotrimer coupling while preserving Gβ1γ2 activation of the effector phospholipase-C β.

Original languageEnglish
Pages (from-to)1086-1094
Number of pages9
Issue number7
StatePublished - 9 Jul 2008




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