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Stable interactions between the transmembrane domains of the adenosine A 2A receptor
Author(s) -
Thévenin Damien,
Lazarova Tzvetana
Publication year - 2008
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1110/ps.034843.108
Subject(s) - circular dichroism , förster resonance energy transfer , transmembrane domain , helix (gastropod) , rhodopsin , chemistry , biophysics , g protein coupled receptor , crystallography , micelle , transmembrane protein , receptor , biochemistry , biology , physics , retinal , ecology , quantum mechanics , snail , aqueous solution , fluorescence
G‐protein‐coupled receptors (GPCRs) must properly insert and fold in the membrane to adopt a stable native structure and become biologically active. The interactions between transmembrane (TM) helices are believed to play a major role in these processes. Previous studies in our group showed that specific interactions between TM helices occur, leading to an increase in helical content, especially in weakly helical TM domains, suggesting that helix–helix interactions in addition to helix–lipid interactions facilitate helix formation. They also demonstrated that TM peptides interact in a similar fashion in micelles and lipid vesicles, as they exhibit relatively similar thermal stability and α‐helicity inserted in SDS micelles to that observed in liposomes. In this study, we perform an analysis of pairwise interactions between peptides corresponding to the seven TM domains of the human A 2A receptor (A 2A R). We used a combination of Förster resonance energy transfer (FRET) measurement and circular dichroism (CD) spectroscopy to detect and analyze these interactions in detergent micelles. We found that strong and specific interactions occur in only seven of the 28 possible peptide pairs. Furthermore, not all interactions, identified by FRET, lead to a change in helicity. Our results identify stabilizing contacts that are likely related to the stability of the receptor and that are consistent with what is known about the three‐dimensional structure and stability of rhodopsin and the β 2 adrenergic receptor.