Solid-state NMR structural investigations of peptide-based nanodiscs and of transmembrane helices in bicellar arrangements.
Fiche publication
Date publication
janvier 2019
Journal
Chemistry and physics of lipids
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BECHINGER Burkhard
Tous les auteurs :
Salnikov ES, Aisenbrey C, Anantharamaiah GM, Bechinger B
Lien Pubmed
Résumé
The membrane topology of the peptide 18 A, 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. 18 A (Ac-DWLKA FYDKV AEKLK EAF- NH) 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 18 A 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 N or H labelled positions of 18 A 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 domain of the DQ alpha-1 domain of the major histocomptability complex (MHC) class II has been prepared and reconstituted into magnetically oriented bicelles for NMR structural analysis.
Mots clés
Apo A-I mimetic, Bicelle, DIBMA polymer, DQA1 of MHC II, DQB1, Oriented bilayer, Rim structure, Solid-state NMR, helix topology
Référence
Chem. Phys. Lipids. 2019 Jan 31;: