Determination of helical membrane protein topology using residual dipolar couplings and exhaustive search algorithm: application to phospholamban.
Dipolar waves are distinct hallmarks of both the secondary and tertiary structures of alpha-helical proteins that are immobilized in membrane bilayers or embedded in anisotropic media. We present a simple, semi-empirical approach that exploits the modulation of the amplitude and average of dipolar waves to determine the topology of alpha-helical proteins. Moreover, we describe the application of this method for the structural determination of a detergent solubilized membrane protein, phospholamban (PLB) that is involved in calcium regulation of cardiac muscle. When combined with high-resolution solid-state NMR data, this method can serve as a fast route for determining the topology of helical membrane proteins solubilized in detergent micelles.
Mascioni
Alessandro
A
Department of Chemistry, University of Minnesota, 207 Pleasant St. S.E. Minneapolis, MN 55455, USA.
Eggimann
Becky L
BL
Veglia
Gianluigi
G
D000465:Algorithms; D001665:Binding Sites; D002135:Calcium-Binding Proteins / Q000032:analysis / Q000737:chemistry*; D003198:Computer Simulation; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008565:Membrane Proteins / Q000032:analysis / Q000737:chemistry*; D008956:Models, Chemical; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D000099211:Phospholamban
D002135:Calcium-Binding Proteins; D008565:Membrane Proteins; D000099211:Phospholamban