title: The presence of membranes or micelles induces structural changes of the myristoylated guanylate-cyclase activating protein-2.
abstract: Guanylate cyclase-activating proteins (GCAPs) are neuronal Ca(2+) sensors that play a central role in shaping the photoreceptor light response and in light adaptation through the Ca(2+)-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.
authors.affiliation: Institute of Medical Physics and Biophysics, University of Leipzig, Härtelstr. 16-18, 04107 Leipzig, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Theisgen
authors.forename: Lars
authors.initials: L
authors.lastname: Thomas
authors.forename: Thomas
authors.initials: T
authors.lastname: Schröder
authors.forename: Christian
authors.initials: C
authors.lastname: Lange
authors.forename: Michael
authors.initials: M
authors.lastname: Kovermann
authors.forename: Jochen
authors.initials: J
authors.lastname: Balbach
authors.forename: Daniel
authors.initials: D
authors.lastname: Huster
mesh_terms: D002135:Calcium-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D051604:Guanylate Cyclase-Activating Proteins / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism; D057927:Hydrophobic and Hydrophilic Interactions; D008051:Lipid Bilayers / Q000737:chemistry / Q000494:pharmacology*; D008081:Liposomes / Q000737:chemistry / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008823:Micelles; D019814:Myristic Acid / Q000737:chemistry / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism; D010713:Phosphatidylcholines / Q000737:chemistry / Q000494:pharmacology; D010786:Photoreceptor Cells / Q000187:drug effects* / Q000378:metabolism; D011485:Protein Binding; D012160:Retina / Q000187:drug effects* / Q000378:metabolism; D013696:Temperature
chemical_list: D002135:Calcium-Binding Proteins; D051604:Guanylate Cyclase-Activating Proteins; D008051:Lipid Bilayers; D008081:Liposomes; D008823:Micelles; D009419:Nerve Tissue Proteins; D010713:Phosphatidylcholines; D019814:Myristic Acid; C028694:1-palmitoyl-2-oleoylphosphatidylcholine