Residue-specific vibrational echoes yield 3D structures of a transmembrane helix dimer

Science. 2011 Jun 3;332(6034):1206-9. doi: 10.1126/science.1202997.

Abstract

Two-dimensional (2D) vibrational echo spectroscopy has previously been applied to structural determination of small peptides. Here we extend the technique to a more complex, biologically important system: the homodimeric transmembrane dimer from the α chain of the integrin α(IIb)β(3). We prepared micelle suspensions of the pair of 30-residue chains that span the membrane in the native structure, with varying levels of heavy ((13)C=(18)O) isotopes substituted in the backbone of the central 10th through 20th positions. The constraints derived from vibrational coupling of the precisely spaced heavy residues led to determination of an optimized structure from a range of model candidates: Glycine residues at the 12th, 15th, and 16th positions form a tertiary contact in parallel right-handed helix dimers with crossing angles of -58° ± 9° and interhelical distances of 7.7 ± 0.5 angstroms. The frequency correlation established the dynamical model used in the analysis, and it indicated the absence of mobile water associated with labeled residues. Delocalization of vibrational excitations between the helices was also quantitatively established.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Motifs
  • Carbon Isotopes
  • Cell Membrane / chemistry*
  • Energy Transfer
  • Micelles
  • Models, Molecular
  • Molecular Dynamics Simulation
  • Oxygen Isotopes
  • Peptides / chemistry*
  • Platelet Membrane Glycoprotein IIb / chemistry*
  • Protein Multimerization
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Spectrophotometry, Infrared
  • Spectroscopy, Fourier Transform Infrared
  • Vibration

Substances

  • Carbon Isotopes
  • Micelles
  • Oxygen Isotopes
  • Peptides
  • Platelet Membrane Glycoprotein IIb