Role of helix 8 in G protein-coupled receptors based on structure-function studies on the type 1 angiotensin receptor

John Huynh, Walter Glen Thomas, Marie -Isabel Aguilar, Leonard Keith Pattenden

Research output: Contribution to journalArticleResearchpeer-review

45 Citations (Scopus)

Abstract

G protein-coupled receptors (GPCRs) are transmembrane receptors that convert extracellular stimuli to intracellular signals. The type 1 angiotensin II receptor is a widely studied GPCR with roles in blood pressure regulation,water and salt balance and cell growth. Thecomplex molecular and structural changes that underpin receptor activation and signaling are the focus of intense research. Increasingly, there is an appreciation that the plasma membrane participates in Receptor function via direct, physical interactions that reciprocally modulate both lipid and receptor and provide microdomains for specialized activities. Reversible protein:lipid interactions are commonly mediated by amphipathic alpha -helices in proteins and one such motif ? a short helix, referred to as helix VIII/8 (H8), located at the start of the carboxyl (C)- terminus of GPCRs ? is gaining recognition for its importance to GPCR function. Here, we review the identification of H8 in GPCRs and examine its capacity to sense and interact with diverse proteins and lipid environment, most notably with acidic lipids that include phosphatidylinositol phosphates.
Original languageEnglish
Pages (from-to)118 - 127
Number of pages10
JournalMolecular and Cellular Endocrinology
Volume302
Issue number2
DOIs
Publication statusPublished - 2009

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