Structure and topology of a peptide segment of the 6th transmembrane domain of the Saccharomyces cerevisae alpha-factor receptor in phospholipid bilayers

Biopolymers. 2001 Oct 5;59(4):243-56. doi: 10.1002/1097-0282(20011005)59:4<243::AID-BIP1021>3.0.CO;2-H.


A detailed analysis of the structure of an 18-residue peptide AQSLLVPSIIFILAYSLK [M6(252-269, C252A)] in 1,2-dimyristoyl-sn-glycero-phosphocholine bilayers was carried out using solid state NMR and attenuated total reflection Fourier transform infrared spectroscopy. The peptide corresponds to a portion of the 6th transmembrane domain of the alpha-factor receptor of Saccharomyces cerevisiae. Ten homologs of M6(252-269, C252A) were synthesized in which individual residues were labeled with (15)N. One- and two-dimensional solid state NMR experiments were used to determine the chemical shifts and (1)H-(15)N dipolar coupling constants for the (15)N-labeled peptides in oriented dimyristoylphosphatidylcholine bilayers on stacked glass plates. These parameters were used to calculate the structure and orientation of M6(252-269, C252A) in the bilayers. The results indicate that the carboxyl terminal residues (9-14) are alpha-helical and oriented with an angle of about 8 degrees with respect to the bilayer normal. Independently, an attenuated total reflection Fourier transform infrared spectroscopy analysis on M6(252-269, C252A) in a 1,2-dimyristoyl-sn-glycero-phosphocholine bilayer concluded that the helix tilt angle was about 12.5 degrees. The results on the structure of M6(252-269, C252A) in bilayers are in good agreement with the structure determined in trifluoroethanol/water solutions (B. Arshava et al. Biopolymers, 1998, Vol. 46, pp. 343-357). The present study shows that solid state NMR spectroscopy can provide high resolution information on the structure of transmembrane domains of a G protein-coupled receptor.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Biopolymers / chemistry
  • Biopolymers / genetics
  • Lipid Bilayers
  • Magnetic Resonance Spectroscopy
  • Mating Factor
  • Models, Molecular
  • Molecular Sequence Data
  • Nitrogen Isotopes
  • Peptides / chemistry
  • Phospholipids
  • Protein Structure, Tertiary
  • Receptors, Mating Factor
  • Receptors, Peptide / chemistry*
  • Receptors, Peptide / genetics
  • Saccharomyces cerevisiae / chemistry
  • Saccharomyces cerevisiae / genetics
  • Spectroscopy, Fourier Transform Infrared
  • Transcription Factors*


  • Biopolymers
  • Lipid Bilayers
  • Nitrogen Isotopes
  • Peptides
  • Phospholipids
  • Receptors, Mating Factor
  • Receptors, Peptide
  • Transcription Factors
  • Mating Factor