Screening molecular associations with lipid membranes using natural abundance 13C cross-polarization magic-angle spinning NMR and principal component analysis.
We describe an NMR approach for detecting the interactions between phospholipid membranes and proteins, peptides, or small molecules. First, 1H-13C dipolar coupling profiles are obtained from hydrated lipid samples at natural isotope abundance using cross-polarization magic-angle spinning NMR methods. Principal component analysis of dipolar coupling profiles for synthetic lipid membranes in the presence of a range of biologically active additives reveals clusters that relate to different modes of interaction of the additives with the lipid bilayer. Finally, by representing profiles from multiple samples in the form of contour plots, it is possible to reveal statistically significant changes in dipolar couplings, which reflect perturbations in the lipid molecules at the membrane surface or within the hydrophobic interior.
Middleton
David A
DA
Department of Biomolecular Sciences, University of Manchester Institute of Science and Technology, P.O. Box 88, Sackville Street, Manchester M60 1QD, United Kingdom. david.a.middleton@umist.ac.uk
Hughes
Eleri
E
Madine
Jillian
J
D002135:Calcium-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D002247:Carbon Isotopes; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D004134:Dimyristoylphosphatidylcholine / Q000737:chemistry; D008563:Membrane Lipids / Q000737:chemistry* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D011107:Polylysine / Q000737:chemistry / Q000378:metabolism; D025341:Principal Component Analysis / Q000379:methods; D014268:Trifluoperazine / Q000737:chemistry / Q000378:metabolism; D000099211:Phospholamban
D002135:Calcium-Binding Proteins; D002247:Carbon Isotopes; D004134:Dimyristoylphosphatidylcholine; D008563:Membrane Lipids; D009419:Nerve Tissue Proteins; D011107:Polylysine; D014268:Trifluoperazine; D000099211:Phospholamban; C029152:G-substrate