Premium
Comparing crystal structures of Ca 2+ ‐ ATP ase in the presence of different lipids
Author(s) -
Drachmann Nikolaj D.,
Olesen Claus,
Møller Jesper V.,
Guo Zheng,
Nissen Poul,
Bublitz Maike
Publication year - 2014
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.12957
Subject(s) - serca , chemistry , thapsigargin , cyclopiazonic acid , endoplasmic reticulum , phospholamban , phosphatidylcholine , p type atpase , biophysics , lipid bilayer , biochemistry , atpase , enzyme , crystallography , biology , membrane , phospholipid
The activity of the sarco/endoplasmic reticulum Ca 2+ ‐ ATP ase ( 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.