title: Detergent properties influence the stability of the glycophorin A transmembrane helix dimer in lysophosphatidylcholine micelles.
abstract: Detergents might affect membrane protein structures by promoting intramolecular interactions that are different from those found in native membrane bilayers, and fine-tuning detergent properties can be crucial for obtaining structural information of intact and functional transmembrane proteins. To systematically investigate the influence of the detergent concentration and acyl-chain length on the stability of a transmembrane protein structure, the stability of the human glycophorin A transmembrane helix dimer has been analyzed in lyso-phosphatidylcholine micelles of different acyl-chain length. While our results indicate that the transmembrane protein is destabilized in detergents with increasing chain-length, the diameter of the hydrophobic micelle core was found to be less crucial. Thus, hydrophobic mismatch appears to be less important in detergent micelles than in lipid bilayers and individual detergent molecules appear to be able to stretch within a micelle to match the hydrophobic thickness of the peptide. However, the stability of the GpA TM helix dimer linearly depends on the aggregation number of the lyso-PC detergents, indicating that not only is the chemistry of the detergent headgroup and acyl-chain region central for classifying a detergent as harsh or mild, but the detergent aggregation number might also be important.
authors.affiliation: Institut für Pharmazie und Biochemie, Johannes Gutenberg-Universität Mainz, Mainz, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Stangl
authors.forename: Anbazhagan
authors.initials: A
authors.lastname: Veerappan
authors.forename: Anja
authors.initials: A
authors.lastname: Kroeger
authors.forename: Peter
authors.initials: P
authors.lastname: Vogel
authors.forename: Dirk
authors.initials: D
authors.lastname: Schneider
mesh_terms: D000595:Amino Acid Sequence; D002462:Cell Membrane / Q000737:chemistry*; D003902:Detergents / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006021:Glycophorins / Q000737:chemistry*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008244:Lysophosphatidylcholines / Q000737:chemistry / Q000494:pharmacology*; D008823:Micelles; D008969:Molecular Sequence Data; D055503:Protein Multimerization / Q000187:drug effects*; D017433:Protein Structure, Secondary / Q000187:drug effects
chemical_list: D003902:Detergents; D006021:Glycophorins; D008244:Lysophosphatidylcholines; D008823:Micelles