Mixing and matching detergents for membrane protein NMR structure determination.
One major obstacle to membrane protein structure determination is the selection of a detergent micelle that mimics the native lipid bilayer. Currently, detergents are selected by exhaustive screening because the effects of protein-detergent interactions on protein structure are poorly understood. In this study, the structure and dynamics of an integral membrane protein in different detergents is investigated by nuclear magnetic resonance (NMR) and electron paramagnetic resonance (EPR) spectroscopy and small-angle X-ray scattering (SAXS). The results suggest that matching of the micelle dimensions to the protein's hydrophobic surface avoids exchange processes that reduce the completeness of the NMR observations. Based on these dimensions, several mixed micelles were designed that improved the completeness of NMR observations. These findings provide a basis for the rational design of mixed micelles that may advance membrane protein structure determination by NMR.
Columbus
Linda
L
Department of Chemistry, University of Virginia, Charlottesville, Virginia 22904, USA. Columbus@virginia.edu
Lipfert
Jan
J
Jambunathan
Kalyani
K
Fox
Daniel A
DA
Sim
Adelene Y L
AY
Doniach
Sebastian
S
Lesley
Scott A
SA
D003902:Detergents / Q000737:chemistry; D008565:Membrane Proteins / Q000737:chemistry*; D008823:Micelles; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D011487:Protein Conformation
D003902:Detergents; D008565:Membrane Proteins; D008823:Micelles