Conformational studies of an amphipathic peptide corresponding to human apolipoprotein A‐II residues 18‐30 with a C‐terminal lipid binding motif EWLNS

Abstract

A peptide was designed and synthesized to enhance the lipid binding properties of a 13-residue fragment of apolipoprotein A-11. The peptide, VTDYGKDLMEKVKEWLNS [apoA-11( 18-30) +], contains a fiveresidue amphipathic motif, EWLNS, at the C-terminus of apolipoprotein A-I1 residues 18-30. The lipid binding properties of apoA-11( 18-30) + were assessed using optical spectroscopy in the presence of sodium dodecyl sulfate (SDS), dodecylphosphocholine (DPC), tetradecyltrimethyl ammonium chloride (TMA) and dimyristoylphosphatidylcholine (DMPC). The fluorescence emission spectra and the circular dichroism data suggested that apoA-11( 18-30) + interacted most strongly with SDS and most weakly with DMPC. An ensemble of structures for apoA-11( 18-30)+ in aqueous solution containing SDS was calculated using distance geometry/simulated annealing methods from 308 NOE-based distance restraints. The backbone (N-C-C= 0) RMSD from the average structure of an ensemble of 15 out of 20 calculated structures was 0.54k0.16 A. Apart from some dynamic fraying at both termini, the distance geometry and simulated annealing calculations showed that apoA-11( 18-30) + adopted a well defined amphipathic helix with distinct hydrophobic and hydrophilic faces. 0 Munksgaard 1996.

NMR of Membrane-Associated Peptides and Proteins

“…Structural studies of apolipoproteins in micelles by NMR were pioneered by him in the early 1990s. Solution structures of several peptides from apoA-I, apoA-II, apoC-I, apoC-II, and apoE in SDS or DPC micelles were determined by 2D NMR techniques [51,52,[111][112][113][115][116][117]. These peptides indeed adopt amphipathic helical structures, providing support for the amphipathic helix model proposed by Segrest [118].…”

Anti-infective activity of apolipoprotein domain derived peptides in vitro: identification of novel antimicrobial peptides related to apolipoprotein B with anti-HIV activity

“…In particular many other apolipoproteins contain amphipathic -helical regions. Apolipoprotein AII (apoAII) contains a region - apoAII(18-30) - which has previously been stabilised as an α-helical peptide by addition of a 5 mer motif to the C-terminal to promote α-helical structure [12]. In a separate study apolipoprotein J (apoJ) was predicted to contain five amphipathic -helical regions, which together allow this apolipoprotein to act as a biological detergent [13].…”