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Biophysics of Proteins at Surfaces: Assembly, Activation, Signaling
Poster Abstracts
1-POS
Board 1
Helix 8 of the Angiotensin-II Type 1a Receptor Interacts With Phosphatidylinositol
Phosphates and Modulates Membrane Insertion
Daniel J. Hirst
1
, Tzong-Hsien Lee
1
, Walter G. Thomas
2
,
Mibel Aguilar
1
.
1
Monash University, Clayton, Australia,
2
The University of Queensland, St Lucia, Vic, Australia.
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 [1] to examine the role of phosphatidylinositdes in the specific recognition of
Helix 8 in the AT1A receptor. A synthetic peptide corresponding to Leu305 to Lys325 (Helix 8
AT1A) discriminated between PIPs and different charges on lipid membranes [2]. 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.
1. Lee TH, Hirst D, and Aguilar MI, ‘New Insights into the Molecular Mechanisms of
Biomembrane Structural Changes and Interactions by optical biosensor technology’, BBA
Biomembranes, in press, 2015. doi: 10.1016/j.bbamem.2015.05.012.
2. Hirst D, Lee TH, Pattenden LK, Thomas WG and Aguilar MI, “Helix 8 of the angiotensin-1a
receptor interacts with phosphatidylinositol phosphates and modulates membrane insertion”.
Scientific Reports, in press, 2015. DOI: 10.1038/srep09972.