Glycine Perturbs Local and Global Conformational Flexibility of a Transmembrane Helix

Biochemistry. 2018 Feb 27;57(8):1326-1337. doi: 10.1021/acs.biochem.7b01197. Epub 2018 Feb 9.


Flexible transmembrane helices frequently support the conformational transitions between different functional states of membrane proteins. While proline is well known to distort and destabilize transmembrane helices, the role of glycine is still debated. Here, we systematically investigated the effect of glycine on transmembrane helix flexibility by placing it at different sites within the otherwise uniform leucine/valine repeat sequence of the LV16 model helix. We show that amide deuterium/hydrogen exchange kinetics are increased near glycine. Molecular dynamics simulations reproduce the measured exchange kinetics and reveal, at atomic resolution, a severe packing defect at glycine that enhances local hydration. Furthermore, glycine alters H-bond occupancies and triggers a redistribution of α-helical and 310-helical H-bonds. These effects facilitate local helix bending at the glycine site and change the collective dynamics of the helix.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Glycine / chemistry*
  • Hydrogen Bonding
  • Kinetics
  • Membrane Proteins / chemistry*
  • Molecular Dynamics Simulation
  • Peptides / chemistry*
  • Protein Conformation
  • Protein Conformation, alpha-Helical
  • Water / chemistry


  • Membrane Proteins
  • Peptides
  • Water
  • Glycine