title: Helix 8 of the angiotensin- II type 1A receptor interacts with phosphatidylinositol phosphates and modulates membrane insertion.
abstract: The carboxyl-terminus of the type 1 angiotensin II receptor (AT1A) regulates receptor activation/deactivation and the amphipathic Helix 8 within the carboxyl-terminus is a high affinity interaction motif for plasma membrane lipids. We have used dual polarisation interferometry (DPI) to examine the role of phosphatidylinositdes in the specific recognition of Helix 8 in the AT1A receptor. A synthetic peptide corresponding to Leu(305) to Lys(325) (Helix 8 AT1A) discriminated between PIPs and different charges on lipid membranes. Peptide binding to PtdIns(4)P-containing bilayers caused a dramatic change in the birefringence (a measure of membrane order) of the bilayer. Kinetic modelling showed that PtdIns(4)P is held above the bilayer until the mass of bound peptide reaches a threshold, after which the peptides insert further into the bilayer. This suggests that Helix 8 can respond to the presence of PI(4)P by withdrawing from the bilayer, resulting in a functional conformational change in the receptor.
authors.affiliation: Department of Biochemistry and Molecular Biology, Monash University, Melbourne 3800 Australia.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Hirst
authors.affiliation: Department of Biochemistry and Molecular Biology, Monash University, Melbourne 3800 Australia.
authors.forename: Tzong-Hsien
authors.initials: TH
authors.lastname: Lee
authors.affiliation: Department of Biochemistry and Molecular Biology, Monash University, Melbourne 3800 Australia.
authors.forename: Leonard K
authors.initials: LK
authors.lastname: Pattenden
authors.affiliation: School of Biomedical Sciences, The University of Queensland, St Lucia, Queensland, 4072 Australia.
authors.forename: Walter G
authors.initials: WG
authors.lastname: Thomas
authors.affiliation: Department of Biochemistry and Molecular Biology, Monash University, Melbourne 3800 Australia.
authors.forename: Marie-Isabel
authors.initials: MI
authors.lastname: Aguilar
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001718:Birefringence; D007368:Interferometry; D007700:Kinetics; D016018:Least-Squares Analysis; D008051:Lipid Bilayers / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010455:Peptides / Q000737:chemistry; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism*; D017433:Protein Structure, Secondary; D044140:Receptor, Angiotensin, Type 1 / Q000737:chemistry* / Q000378:metabolism*; D013329:Structure-Activity Relationship; D034421:Sus scrofa; D013997:Time Factors
chemical_list: D008051:Lipid Bilayers; D010455:Peptides; D018129:Phosphatidylinositol Phosphates; D044140:Receptor, Angiotensin, Type 1