title: Comparing crystal structures of Ca(2+) -ATPase in the presence of different lipids.
abstract: The activity of the sarco/endoplasmic reticulum Ca(2+) -ATPase (SERCA) depends strongly on the lipid composition of the surrounding membrane. Yet, structural information on SERCA-lipid interaction is still relatively scarce, and the influence of different lipids on the enzyme is not well understood. We have analyzed SERCA crystal structures in the presence of four different phosphatidylcholine lipids of different lengths and double-bond compositions, and we find three different binding sites for lipid head groups, which are apparently independent of the acyl moiety of the lipids used. By comparison with other available SERCA structures with bound lipids, we find a total of five recurring sites, two of which are specific to certain conformational states of the enzyme, two others are state-independent, and one is a crucial site for crystal formation. Three of the binding sites overlap with or are in close vicinity to known binding sites for various SERCA-specific inhibitors and regulators, e.g. thapsigargin, sarcolipin/phospholamban and cyclopiazonic acid. Whereas the transient sites are amenable to a transient, regulatory influence of lipid molecules, the state-independent sites probably provide a flexible anchoring of the protein in the fluid bilayer.
authors.affiliation: Centre for Membrane Pumps in Cells and Disease - PUMPkin, Danish National Research Foundation, Aarhus, Denmark; Department of Molecular Biology and Genetics, Aarhus University, Denmark.
authors.forename: Nikolaj D
authors.initials: ND
authors.lastname: Drachmann
authors.forename: Claus
authors.initials: C
authors.lastname: Olesen
authors.forename: Jesper V
authors.initials: JV
authors.lastname: Møller
authors.forename: Zheng
authors.initials: Z
authors.lastname: Guo
authors.forename: Poul
authors.initials: P
authors.lastname: Nissen
authors.forename: Maike
authors.initials: M
authors.lastname: Bublitz
mesh_terms: D000818:Animals; D018360:Crystallography, X-Ray; D003840:Deoxycholic Acid / Q000737:chemistry; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D010713:Phosphatidylcholines / Q000737:chemistry*; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011817:Rabbits; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000737:chemistry*
chemical_list: D010713:Phosphatidylcholines; D003840:Deoxycholic Acid; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; C017251:1,2-oleoylphosphatidylcholine
keywords: Ca2+-ATPase; P-type ATPase; SERCA; lipid-protein interaction; membrane protein