title: Detergents modulate dimerization, but not helicity, of the glycophorin A transmembrane domain.
abstract: Understanding how the lipid environment influences transmembrane helix association requires thermodynamic measurements that can be interpreted in terms of specific chemical interactions. We have used Förster resonance energy transfer to measure dimerization of the glycophorin A transmembrane helix in detergent micelles. The observed Kd is at least two orders of magnitude weaker in sodium dodecyl sulfate than it is in zwitterionic detergents. In contrast, neither dimerization nor the detergent affects the secondary structure of the glycophorin A helix as measured by far-UV circular dichroism. These measurements support a long standing assumption about the glycophorin A transmembrane domain, that detergents uncouple helix formation from helix dimerization. The approach is applicable to a variety of systems in diverse environments, extending our ability to measure how interactions with complex solvents affect the thermodynamics of oligomerization.
authors.affiliation: Department of Chemistry, Yale University, New Haven, CT, USA.
authors.forename: L E
authors.initials: LE
authors.lastname: Fisher
authors.forename: D M
authors.initials: DM
authors.lastname: Engelman
authors.forename: J N
authors.initials: JN
authors.lastname: Sturgis
mesh_terms: D000595:Amino Acid Sequence; D002087:Butyrates / Q000737:chemistry / Q000494:pharmacology; D002942:Circular Dichroism; D003902:Detergents / Q000737:chemistry / Q000494:pharmacology*; D019281:Dimerization; D004735:Energy Transfer; D005456:Fluorescent Dyes; D006021:Glycophorins / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008823:Micelles; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism*; D010767:Phosphorylcholine / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D017433:Protein Structure, Secondary; D000644:Quaternary Ammonium Compounds / Q000737:chemistry / Q000494:pharmacology; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry / Q000494:pharmacology; D012997:Solvents; D013050:Spectrometry, Fluorescence; D013816:Thermodynamics
chemical_list: C093272:(N-dodecyl-N,N-dimethylammonio)butyric acid; D002087:Butyrates; D003902:Detergents; D005456:Fluorescent Dyes; D006021:Glycophorins; D008823:Micelles; D010446:Peptide Fragments; D000644:Quaternary Ammonium Compounds; D012997:Solvents; D010767:Phosphorylcholine; D012967:Sodium Dodecyl Sulfate; C028810:dodecylphosphocholine