Proline-induced distortions of transmembrane helices

J Mol Biol. 2002 Nov 8;323(5):951-60. doi: 10.1016/s0022-2836(02)01006-9.

Abstract

Proline residues in the transmembrane (TM) alpha-helices of integral membrane proteins have long been suspected to play a key role for helix packing and signal transduction by inducing regions of helix distortion and/or dynamic flexibility (hinges). In this study we try to characterise the effect of proline on the geometric properties of TM alpha-helices. We have examined 199 transmembrane alpha-helices from polytopic membrane proteins of known structure. After examining the location of proline residues within the amino acid sequences of TM helices, we estimated the helix axes either side of a hinge and hence identified a hinge residue. This enabled us to calculate helix kink and swivel angles. The results of this analysis show that proline residues occur with a significant concentration in the centre of sequences of TM alpha-helices. In this location, they may induce formation of molecular hinges, located on average about four residues N-terminal to the proline residue. A superposition of proline-containing TM helices structures shows that the distortion induced is anisotropic and favours certain relative orientations (defined by helix kink and swivel angles) of the two helix segments.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Animals
  • Anisotropy
  • Computer Simulation
  • Databases, Protein
  • Glycine / chemistry
  • Membrane Proteins / chemistry*
  • Models, Molecular
  • Proline / chemistry*
  • Protein Structure, Secondary
  • Software

Substances

  • Membrane Proteins
  • Proline
  • Glycine