title: The membrane environment modulates self-association of the human GpA TM domain--implications for membrane protein folding and transmembrane signaling.
abstract: The influence of lipid bilayer properties on a defined and sequence-specific transmembrane helix-helix interaction is not well characterized yet. To study the potential impact of changing bilayer properties on a sequence-specific transmembrane helix-helix interaction, we have traced the association of fluorescent-labeled glycophorin A transmembrane peptides by fluorescence spectroscopy in model membranes with varying lipid compositions. The observed changes of the glycophorin A dimerization propensities in different lipid bilayers suggest that the lipid bilayer thickness severely influences the monomer-dimer equilibrium of this transmembrane domain, and dimerization was most efficient under hydrophobic matching conditions. Moreover, cholesterol considerably promotes self-association of transmembrane helices in model membranes by affecting the lipid acyl chain ordering. In general, the order of the lipid acyl chains appears to be an important factor involved in determining the strength and stability of transmembrane helix-helix interactions. As discussed, the described influences of membrane properties on transmembrane helix-helix interactions are highly important for understanding the mechanism of transmembrane protein folding and functioning as well as for gaining a deeper insight into the regulation of signal transduction via membrane integral proteins by bilayer properties.
authors.affiliation: Institut für Pharmazie und Biochemie, Johannes Gutenberg-Universität Mainz, Johann-Joachim-Becher-Weg 30, 55128 Mainz, Germany.
authors.forename: Veerappan
authors.initials: V
authors.lastname: Anbazhagan
authors.forename: Dirk
authors.initials: D
authors.lastname: Schneider
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D002784:Cholesterol / Q000737:chemistry; D031541:Fluorescence Resonance Energy Transfer; D006021:Glycophorins / Q000737:chemistry*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008051:Lipid Bilayers / Q000737:chemistry*; D008563:Membrane Lipids / Q000737:chemistry; D008565:Membrane Proteins / Q000737:chemistry*; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D010713:Phosphatidylcholines / Q000737:chemistry; D017510:Protein Folding; D055503:Protein Multimerization; D015398:Signal Transduction; D013050:Spectrometry, Fluorescence; D013696:Temperature
chemical_list: D006021:Glycophorins; D008051:Lipid Bilayers; D008563:Membrane Lipids; D008565:Membrane Proteins; D010455:Peptides; D010713:Phosphatidylcholines; D002784:Cholesterol