Influence of the g- conformation of Ser and Thr on the structure of transmembrane helices

J Struct Biol. 2010 Jan;169(1):116-23. doi: 10.1016/j.jsb.2009.09.009. Epub 2009 Sep 17.


In order to study the influence of Ser and Thr on the structure of transmembrane helices we have analyzed a database of helix stretches extracted from crystal structures of membrane proteins and an ensemble of model helices generated by molecular dynamics simulations. Both complementary analyses show that Ser and Thr in the g- conformation induce and/or stabilize a structural distortion in the helix backbone. Using quantum mechanical calculations, we have attributed this effect to the electrostatic repulsion between the side chain Ogamma atom of Ser and Thr and the backbone carbonyl oxygen at position i-3. In order to minimize the repulsive force between these negatively charged oxygens, there is a modest increase of the helix bend angle as well as a local opening of the helix turn preceding Ser/Thr. This small distortion can be amplified through the helix, resulting in a significant displacement of the residues located at the other side of the helix. The crystal structures of aquaporin Z and the beta(2)-adrenergic receptor are used to illustrate these effects. Ser/Thr-induced structural distortions can be implicated in processes as diverse as ligand recognition, protein function and protein folding.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aquaporins / chemistry
  • Escherichia coli Proteins / chemistry
  • Membrane Proteins / chemistry*
  • Models, Molecular
  • Molecular Dynamics Simulation
  • Protein Structure, Secondary
  • Receptors, Adrenergic, beta-2 / chemistry
  • Serine / chemistry
  • Serine / physiology
  • Structure-Activity Relationship
  • Threonine / chemistry
  • Threonine / physiology


  • Aquaporins
  • Escherichia coli Proteins
  • Membrane Proteins
  • Receptors, Adrenergic, beta-2
  • aqpZ protein, E coli
  • Threonine
  • Serine