The glycophorin A transmembrane domain dimer: sequence-specific propensity for a right-handed supercoil of helices.
Recent studies suggest specific roles for transmembrane helix association in a range of functions, but understanding of the conformation and energetics of these interactions has been elusive. We have studied the specific dimerization of the transmembrane helix of glycophorin A by calculating the minimized interaction energies of a large number of conformations using simulated annealing techniques and tested the models against mutational analysis data. We find that the dimer is best modeled as a right-handed supercoil with an extensive region of close packing along the dimer interface. Furthermore, we observe a sequence-specific propensity for a right-handed supercoil to form when starting the simulated annealing modeling from a dimer of helices with parallel axes, in contrast with the dimerization region of the transcription factor GCN4 which shows a high propensity for the more prevalent left-handed supercoiling.
Treutlein
H R
HR
Howard Hughes Medical Institute, Yale University, New Haven, Connecticut 06511.
Lemmon
M A
MA
Engelman
D M
DM
Brünger
A T
AT
D000595:Amino Acid Sequence; D002462:Cell Membrane / Q000737:chemistry; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004563:Electrochemistry; D006021:Glycophorins / Q000737:chemistry*; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000737:chemistry; D008969:Molecular Sequence Data; D016296:Mutagenesis; D010446:Peptide Fragments / Q000737:chemistry; D017433:Protein Structure, Secondary
D006021:Glycophorins; D046911:Macromolecular Substances; D008565:Membrane Proteins; D010446:Peptide Fragments