Molecular dynamics simulations reveal specific interactions of post-translational palmitoyl modifications with rhodopsin in membranes

Bjoern E S Olausson, Alan Grossfield, Michael C. Pitman, Michael F Brown, Scott E. Feller, Alexander Vogel

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

We present a detailed analysis of the behavior of the highly flexible post-translational lipid modifications of rhodopsin from multiple-microsecond all-atom molecular dynamics simulations. Rhodopsin was studied in a realistic membrane environment that includes cholesterol, as well as saturated and polyunsaturated lipids with phosphocholine and phosphoethanolamine headgroups. The simulation reveals striking differences between the palmitoylations at Cys322 and Cys323 as well as between the palmitoyl chains and the neighboring lipids. Notably the palmitoyl group at Cys322 shows considerably greater contact with helix H1 of rhodopsin, yielding frequent chain upturns with longer reorientational correlation times, and relatively low order parameters. While the palmitoylation at Cys323 makes fewer protein contacts and has increased order compared to Cys322, it nevertheless exhibits greater flexibility with smaller order parameters than the stearoyl chains of the surrounding lipids. The dynamical structure of the palmitoylations - as well as their extensive fluctuations - suggests a complex function for the post-translational modifications in rhodopsin and potentially other G protein-coupled receptors, going beyond their role as membrane anchoring elements. Rather, we propose that the palmitoylation at Cys323 has a potential role as a lipid anchor, whereas the palmitoyl-protein interaction observed for Cys322 suggests a more specific interaction that affects the stability of the dark state of rhodopsin.

Original languageEnglish (US)
Pages (from-to)4324-4331
Number of pages8
JournalJournal of the American Chemical Society
Volume134
Issue number9
DOIs
StatePublished - Mar 7 2012

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Rhodopsin
Lipoylation
Molecular Dynamics Simulation
Post Translational Protein Processing
Lipids
Molecular dynamics
Membranes
Computer simulation
Proteins
Phosphorylcholine
Cholesterol
G-Protein-Coupled Receptors
Anchors
Atoms

ASJC Scopus subject areas

  • Chemistry(all)
  • Catalysis
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

Molecular dynamics simulations reveal specific interactions of post-translational palmitoyl modifications with rhodopsin in membranes. / Olausson, Bjoern E S; Grossfield, Alan; Pitman, Michael C.; Brown, Michael F; Feller, Scott E.; Vogel, Alexander.

In: Journal of the American Chemical Society, Vol. 134, No. 9, 07.03.2012, p. 4324-4331.

Research output: Contribution to journalArticle

Olausson, Bjoern E S ; Grossfield, Alan ; Pitman, Michael C. ; Brown, Michael F ; Feller, Scott E. ; Vogel, Alexander. / Molecular dynamics simulations reveal specific interactions of post-translational palmitoyl modifications with rhodopsin in membranes. In: Journal of the American Chemical Society. 2012 ; Vol. 134, No. 9. pp. 4324-4331.
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