title: Mutual adaptation of a membrane protein and its lipid bilayer during conformational changes.
abstract: The structural elucidation of membrane proteins continues to gather pace, but we know little about their molecular interactions with the lipid environment or how they interact with the surrounding bilayer. Here, with the aid of low-resolution X-ray crystallography, we present direct structural information on membrane interfaces as delineated by lipid phosphate groups surrounding the sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) in its phosphorylated and dephosphorylated Ca(2+)-free forms. The protein-lipid interactions are further analysed using molecular dynamics simulations. We find that SERCA adapts to membranes of different hydrophobic thicknesses by inducing local deformations in the lipid bilayers and by undergoing small rearrangements of the amino-acid side chains and helix tilts. These mutually adaptive interactions allow smooth transitions through large conformational changes associated with the transport cycle of SERCA, a strategy that may be of general nature for many membrane proteins.
authors.affiliation: Centre for Membrane Pumps in Cells and Disease - PUMPKIN, Danish National Research Foundation, DK-8000 Aarhus C, Denmark.
authors.forename: Yonathan
authors.initials: Y
authors.lastname: Sonntag
authors.forename: Maria
authors.initials: M
authors.lastname: Musgaard
authors.forename: Claus
authors.initials: C
authors.lastname: Olesen
authors.forename: Birgit
authors.initials: B
authors.lastname: Schiøtt
authors.forename: Jesper Vuust
authors.initials: JV
authors.lastname: Møller
authors.forename: Poul
authors.initials: P
authors.lastname: Nissen
authors.forename: Lea
authors.initials: L
authors.lastname: Thøgersen
mesh_terms: D018360:Crystallography, X-Ray; D057927:Hydrophobic and Hydrophilic Interactions; D008051:Lipid Bilayers / Q000737:chemistry; D008958:Models, Molecular; D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation; D010766:Phosphorylation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000737:chemistry*
chemical_list: D008051:Lipid Bilayers; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases