European Biophysics Journal

, Volume 40, Issue 4, pp 565–576 | Cite as

The presence of membranes or micelles induces structural changes of the myristoylated guanylate-cyclase activating protein-2

  • Stephan Theisgen
  • Lars Thomas
  • Thomas Schröder
  • Christian Lange
  • Michael Kovermann
  • Jochen Balbach
  • Daniel Huster
Original Paper


Guanylate cyclase-activating proteins (GCAPs) are neuronal Ca2+ sensors that play a central role in shaping the photoreceptor light response and in light adaptation through the Ca2+-dependent regulation of the transmembrane retinal guanylate cyclase. GCAPs are N-terminally myristoylated, and the role of the myristoyl moiety is not yet fully understood. While protein lipid chains typically represent membrane anchors, the crystal structure of GCAP-1 showed that the myristoyl chain of the protein is completely buried within a hydrophobic pocket of the protein, which stabilizes the protein structure. Therefore, we address the question of the localization of the myristoyl group of GCAP-2 in the absence and in the presence of lipid membranes as well as DPC detergents (as a membrane substitute amenable to solution state NMR). We investigate membrane binding of both myristoylated and nonmyristoylated GCAP-2 and study the structure and dynamics of the myristoyl moiety of GCAP-2 in the presence of POPC membranes. Further, we address structural alterations within the myristoylated N-terminus of GCAP-2 in the presence of membrane mimetics. Our results suggest that upon membrane binding the myristoyl group is released from the protein interior and inserts into the lipid bilayer.


Lipid modification GCAP-2 Membrane-protein interaction Order parameter 



Guanylate cyclase


Guanylate cyclase-activating protein-2


Neuronal calcium sensor


Heteronuclear single quantum coherence






Isopropyl β-d-1-thiogalactopyranoside


Optical density




Cyclic GMP




Ethylenediaminetetraacetic acid


High performance liquid chromatography


Free induction decay


Trifluoroacetic acid


Insensitive nuclei enhanced by polarization transfer




3-(N-morpholino)propanesulfonic acid


2-(N-morpholino)ethanesulfonic acid




4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid


Protein databank


Nuclear magnetic resonance


Molecular weight cut-off




Water suppression by gradient-tailored excitation


Globally optimized alternating phase rectangular pulse


Wideband alternating-phase low-power technique for zero-residual-splitting


Critical micelle concentration



This work was supported by a grant from the Deutsche Forschungsgemeinschaft (DFG, HU 720/10-1). M.K. and J.B. were supported by grants from DFG (SFB 610) and J.B. by the Exzellenznetzwerk Biowissenschaften of Sachsen-Anhalt. J.B. thanks the European Development Fund of the European Union.


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Copyright information

© European Biophysical Societies' Association 2011

Authors and Affiliations

  • Stephan Theisgen
    • 1
  • Lars Thomas
    • 1
  • Thomas Schröder
    • 2
  • Christian Lange
    • 2
  • Michael Kovermann
    • 3
  • Jochen Balbach
    • 3
  • Daniel Huster
    • 1
  1. 1.Institute of Medical Physics and BiophysicsUniversity of LeipzigLeipzigGermany
  2. 2.Institute of Biochemistry/BiotechnologyMartin-Luther-University Halle-WittenbergHalle (Saale)Germany
  3. 3.Biophysics Research GroupMartin-Luther-University Halle-WittenbergHalle (Saale)Germany

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