Function of the delipidated β‐adrenergic receptor appears to require a fatty acid or a neutral lipid in addition to phospholipids

Detergent‐solubilized preparations of the β‐adrenergic receptor (R) and of the guanyl nucleotide binding proteins (Gs) were extensively treated to remove phospholipids and cholesterol. Reconstitution of an R‐Gs system was subsequently performed in the presence of a mixture of natural phosphatidyleth...

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Published inEuropean journal of biochemistry Vol. 166; no. 1; pp. 221 - 228
Main Authors KIRILOVSKY, Jorge, EIMERL, Sara, STEINER‐MORDOCH, Sonia, SCHRAMM, Michael
Format Journal Article
LanguageEnglish
Published Oxford, UK Blackwell Publishing Ltd 01.07.1987
Blackwell
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Summary:Detergent‐solubilized preparations of the β‐adrenergic receptor (R) and of the guanyl nucleotide binding proteins (Gs) were extensively treated to remove phospholipids and cholesterol. Reconstitution of an R‐Gs system was subsequently performed in the presence of a mixture of natural phosphatidylethanolamine, phosphatidylcholine and phosphatidylserine or the synthetic dioleoyl derivatives of the same phospholipids. In both cases, an additional lipid was required for the agonist‐dependent activation of Gs. The requirement could be fulfilled by α‐tocopherol, or by unsaturated fatty acids such as oleic acid. Inclusion of this non‐phosphorylated lipid in the reconstituted system enhanced the isoproterenol‐dependent activation of Gs by guanosine 5′‐O‐[γ‐thio]triphosphate 16–33‐fold. The rate of activation was largely dependent on the addition of the agonist. Efficient functional reconstitution of R‐Gs was thus achieved in a totally defined lipid system. Additional studies of the reconstituted system and of the native membrane led to the notion that the non‐phosphorylated lipid plays a role in the function of the hormone‐R complex.
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ISSN:0014-2956
1432-1033
DOI:10.1111/j.1432-1033.1987.tb13505.x