Structure of the parathyroid hormone receptor C terminus bound to the G-protein dimer Gbeta1gamma2.
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Johnston CA, Kimple AJ, Giguere PM, Siderovski DP
Structure of the parathyroid hormone receptor C terminus bound to the G-protein dimer Gbeta1gamma2.
Structure. 2008 Jul;16(7):1086-94. doi: 10.1016/j.str.2008.04.010.
- PubMed ID
- 18611381 [ View in PubMed]
- Abstract
A critical role of the Gbetagamma dimer in heterotrimeric G-protein signaling is to facilitate the engagement and activation of the Galpha subunit by cell-surface G-protein-coupled receptors. However, high-resolution structural information of the connectivity between receptor and the Gbetagamma dimer has not previously been available. Here, we describe the structural determinants of Gbeta1gamma2 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 Gbeta residues located within the outer edge of WD1- and WD7-repeat segments of the Gbeta toroid structure. These regions encompass a predicted membrane-facing region of Gbeta thought to be oriented in a fashion that is accessible to the membrane-spanning receptor. Mutation of key receptor contact residues on Gbeta1 leads to a selective loss of function in receptor/heterotrimer coupling while preserving Gbeta1gamma2 activation of the effector phospholipase-C beta.