Solid-state NMR structural investigations of peptide-based nanodiscs and of transmembrane helices in bicellar arrangements. (March 2019)

• Record Type: Journal Article
• Authors: Salnikov, Evgeniy S.; Aisenbrey, Christopher; Anantharamaiah, G.M.; Bechinger, Burkhard
• Is Part Of: Chemistry and physics of lipids. Volume 219(2019)
• Page Start: 58
• Page End: 71
• Publication Date: 2019-03
• Subjects: CHAPS 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate -- CHAPSO 3-[(3-cholamidopropyl)dimethylammonio]-2-hydroxy-1-propanesulfonate -- DIBMA diisobutylene/maleic acid copolymer -- DHPC 1, 2-di-hexanoyl-sn-glycero-3-phosphocholine -- DMPC 1, 2-di-myristoyl-sn-glycero-3-phosphocholine -- HDL high density lipoprotein -- HFIP hexafluoro isopropanol -- LWHH line width at half height -- MAS magic angle spinning -- MSP membrane scaffolding protein -- NMR nuclear magnetic resonance -- PC phosphatidylcholine -- POPC 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine -- SMA styrene maleic acid copolymer -- 14A peptide with the sequence Ac-DYLKA FYDKL KEAF- NH2 -- 18A peptide with the sequence Ac-DWLKA FYDKV AEKLK EAF- NH2; Oriented bilayer -- Bicelle -- Solid-state NMR -- helix topology -- Apo A-I mimetic -- Rim structure -- DIBMA polymer -- DQA1 of MHC II -- DQB1; Lipids -- Periodicals; Lipids -- Periodicals; Lipides -- Périodiques; Lipids; Periodicals; Electronic journals; 547.77
• DOI: 10.1016/j.chemphyslip.2019.01.012
• Languages: English
• ISSNs: 0009-3084

Abstract

Highlights: Double-belt arrangement of the rim structure of peptide nanodiscs. Insights into the supramolecular arrangement of HDL. Magnetically oriented DIBMA nanodiscs. Solid-state NMR spectra of a transmembrane domain of the MHC class II receptor. Abstract: The membrane topology of the peptide 18A, a derivative of apolipoprotein A-I, is investigated in structural detail. Apolipoprotein A-I is the dominant protein component of high density lipoproteins with important functions in cholesterol metabolism. 18A (Ac-DWLKA FYDKV AEKLK EAF- NH2 ) was designed to mimic the structure of tandem domains of class A amphipathic helices and has served as a lead peptide for biomedical applications. At low peptide-to-lipid ratios 18A partitions into phosphatidylcholine membranes with helix topologies parallel to the membrane surface, an alignment that is maintained when disc-like bicelles form at higher peptide-to-lipid ratios. Notably, the bicelles interact cooperatively with the magnetic field of the NMR spectrometer, thus the bilayer normal is oriented perpendicular to the magnetic field direction. A set of peptides that totals four 15 N or 2 H labelled positions of 18A allowed the accurate analysis of tilt and azimuthal angles relative to the membrane surface under different conditions. The topology agrees with a double belt arrangement forming a rim that covers the hydrophobic fatty acyl chains of the bicelles. In another set of experiments, it was shown that POPC nanodiscs prepared in the presence of diisobutylene/maleic acid (DIBMA) polymers can also be made to align in the magnetic field. Finally, the transmembrane domains of the DQ alpha-1 and DQ beta-1 subunits of the major histocomptability complex (MHC) class II have been prepared and reconstituted into magnetically oriented bicelles for NMR structural analysis.