Glycine Perturbs Local and Global Conformational Flexibility of a Transmembrane Helix

Research output: Contribution to journalJournal articleResearchpeer-review

  • Philipp Högel
  • Alexander Götz
  • Felix Kuhne
  • Maximilian Ebert
  • Walter Stelzer
  • Rand, Kasper Dyrberg
  • Christina Scharnagl
  • Dieter Langosch

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.

Original languageEnglish
JournalBiochemistry
Volume57
Issue number8
Pages (from-to)1326-1337
Number of pages12
ISSN0006-2960
DOIs
Publication statusPublished - 27 Feb 2018

ID: 195553900