Tilt angle of a trans-membrane helix is determined by hydrophobic mismatch

J Mol Biol. 2005 Jul 8;350(2):310-8. doi: 10.1016/j.jmb.2005.05.004.

Abstract

In order to investigate the compensation mechanism of a trans-membrane helix in response to hydrophobic mismatch, the tilt and rotation angles of the trans-membrane helix of Vpu aligned in lipid bilayers of various thickness were determined using orientation-dependent frequencies obtained from solid-state NMR experiments of aligned samples. A tilt angle of 18 degrees was observed in 18:1-O-PC/DOPG (9:1) lipid bilayers, which have a hydrophobic thickness that approximately matches the hydrophobic length of the trans-membrane helix of Vpu. Upon decreasing the hydrophobic thickness of lipid bilayers, no significant change in rotation angle was observed. However, the tilt angle increased systematically with increasing positive mismatch to 27 degrees in 14:0-O-PC/DMPG (9:1), 35 degrees in 12:0-O-PC/DLPG (9:1), and 51 degrees in 10:0 PC/10:0 PG (9:1) lipid bilayers, indicating that the change in tilt angle of the trans-membrane helix is a principal compensation mechanism for hydrophobic mismatch. In addition, the distinctive kink in the middle of the helix observed in 18:1 bilayers disappears in thinner bilayers. Although the opposite of what might be expected, this finding suggests that a helix kink may also be a part of the hydrophobic matching mechanism for trans-membrane helices.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Cell Membrane / chemistry
  • Cell Membrane / metabolism
  • HIV-1 / chemistry*
  • Human Immunodeficiency Virus Proteins
  • Hydrophobic and Hydrophilic Interactions
  • Lipid Bilayers / chemistry*
  • Lipid Bilayers / metabolism*
  • Magnetic Resonance Spectroscopy
  • Molecular Sequence Data
  • Protein Structure, Secondary
  • Rotation
  • Viral Regulatory and Accessory Proteins / chemistry*
  • Viral Regulatory and Accessory Proteins / metabolism*

Substances

  • Human Immunodeficiency Virus Proteins
  • Lipid Bilayers
  • Viral Regulatory and Accessory Proteins
  • vpu protein, Human immunodeficiency virus 1