Dynamic membrane protein topological switching upon changes in phospholipid environment
Understanding how a protein sequence folds and orients in a lipid bilayer is central to establishing the molecular basis for membrane protein organization. How lipid environment affects membrane protein organization is understudied. We established that membrane protein orientation is dynamic during and after assembly, dependent on membrane lipid composition, and independent of other cellular factors. We developed a proteoliposome system in which lipid composition can be controlled before and after membrane protein reconstitution and used it to assess the kinetics of changes in transmembrane domain (TMD) orientation and phospholipid flipping within the lipid bilayer triggered by a change in lipid composition. We demonstrate that membrane proteins can undergo rapid postassembly TMD flipping in response to changes in the lipid environment.
Proceedings of the National Academy of Science
- Pub Date:
- November 2015