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PAPERS

Interaction of transmembrane-spanning segments of the α2-adrenergic receptor with model membranes

, , , , , , & show all
Pages 265-278 | Received 19 Nov 2008, Published online: 19 Sep 2009
 

Abstract

Adrenergic receptors are integral membrane proteins involved in cellular signalling that belong to the G protein-coupled receptors. Synthetic peptides resembling the putative transmembrane (TM) segments TM4, TM6 and TM7, of the human α2-adrenergic receptor subtype C10 (P08913) and defined lipid vesicles were used to assess protein-lipid interactions that might be relevant to receptor structure/function. P6 peptide contains the hydrophobic core of TM6 plus the N-terminal hydrophilic motif REKR, while peptides P4 and P7 contained just the hydrophobic stretches of TM4 and TM7, respectively. All the peptides increase their helical tendency at moderate concentrations of TFE (30–50%) and in presence of 1,2-dielaidoyl-sn-glycero-3-phosphatidylethanolamine (DEPE) lipids. However, only P6 displays up to 19% of α-helix in the presence of just the DEPE lipids, evidences a transmembrane orientation and stabilizes the Lα lipid phase. Conversely, P4 and P7 peptides form only stable β-sheet structures in DEPE and favour the non-lamellar, inverted hexagonal (HII) phase of DEPE by lowering its phase transition temperature. This study highlights the potential of using synthetic peptides derived from the amino acid sequence in the native proteins as templates to understand the behaviour of the transmembrane segments and underline the importance of interfacial anchoring interactions to meet hydrophobic matching requirements and define membrane organization.

Abbreviations
GPCR=

G protein-coupled receptor

AR=

Adrenergic receptor

α2-AR=

α2-adrenergic receptor

TM=

transmembrane segment

TMH=

membrane-spanning α-helix

PE=

phosphatidylethanolamine

DEPE=

1,2-dielaidoyl-sn-glycero-3-phosphatidylethanolamine

DPPC=

1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine

MLV=

multilamellar lipid vesicles

Lβ=

gel lamellar phase

Lα=

liquid-crystalline lamellar phase

HII=

inverted hexagonal phase

d=

lattice space

Tm=

gel-to-liquid lamellar phase transition temperature

TH=

lamellar-to-inverted hexagonal phase transition temperature

Abbreviations
GPCR=

G protein-coupled receptor

AR=

Adrenergic receptor

α2-AR=

α2-adrenergic receptor

TM=

transmembrane segment

TMH=

membrane-spanning α-helix

PE=

phosphatidylethanolamine

DEPE=

1,2-dielaidoyl-sn-glycero-3-phosphatidylethanolamine

DPPC=

1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine

MLV=

multilamellar lipid vesicles

Lβ=

gel lamellar phase

Lα=

liquid-crystalline lamellar phase

HII=

inverted hexagonal phase

d=

lattice space

Tm=

gel-to-liquid lamellar phase transition temperature

TH=

lamellar-to-inverted hexagonal phase transition temperature

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