Acyl Transfer from Membrane Lipids to Peptides Is a Generic Process

Abstract

. (2013) 'Acyl transfer from membrane lipids to peptides is a generic process.', Journal of molecular biology., 425 (22). pp. 4379-4387. Further information on publisher's website:http://dx.doi.org/10. 1016/j.jmb.2013.07.013 Publisher's copyright statement: NOTICE: this is the author's version of a work that was accepted for publication in Journal of molecular biology. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reected in this document. Changes may have been made to this work since it was submitted for publication. A denitive version was subsequently published in Journal of molecular biology, 425, 22, 2013, 10.1016/j.jmb.2013.07.013 Additional information: Use policyThe full-text may be used and/or reproduced, and given to third parties in any format or medium, without prior permission or charge, for personal research or study, educational, or not-for-prot purposes provided that:• a full bibliographic reference is made to the original source • a link is made to the metadata record in DRO • the full-text is not changed in any way The full-text must not be sold in any format or medium without the formal permission of the copyright holders.Please consult the full DRO policy for further details. Abstract: The generality of acyl transfer from phospholipids to membrane-active peptides has been probed using liquid chromatography-mass spectrometry (LC-MS) analysis of peptide-lipid mixtures. The peptides examined include melittin, magainin II, PGLa, LAK1, LAK3 and penetratin. Peptides were added to liposomes with membrane lipid compositions ranging from pure phosphatidylcholine (PC) to mixtures of PC with phosphatidylethanolamine (PE), phosphatidylserine (PS) or phosphatidylglycerol (PG). Experiments were typically conducted at pH 7.4 at modest salt concentrations (90 mM NaCl). In favorable cases, lipidated peptides were further characterised by tandem MS methods to determine the sites of acylation. Melittin and magainin II were the most reactive peptides, with significant acyl transfer detected under all conditions and membrane compositions. Both peptides were lipidated at the N-terminus by transfer from PC, PE, PS or PG, as well as at internal sites: lysine for melittin; serine and lysine for magainin II. Acyl transfer could be detected within 3 hours of melittin addition to negatively charged membranes. The other peptides were less reactive, but for each peptide, acylation was found to occur in at least one of the conditions examined. The data demonstrate that acyl transfer is a generic process for peptides bound to membranes composed of diacylglycerophospholipids. Phospholipid membranes cannot therefore be considered as chemically inert towards peptides, and by extension proteins. *Graphical Abstract (for review)HIGHLIGHTS  The scope of acyl transfer from lipids to peptides has been probed  Melittin undergoes lipidation over a broad range of conditions  Magainin II is readily lipidated, bu...

The lipidation profile of aquaporin-0 correlates with the acyl composition of phosphoethanolamine lipids in lens membranes

“…S15, Table S10). K238 lies at the boundary between polar and non-polar surfaces of the helix, a feature that is known to promote acyl transfer from lipids to peptides that localize interfacially [1].…”

“…The quality of this correlation is striking for each family of acyl modified peptides from AQP0 ([234-259] for b-AQP0, for h-AQP0, [1][2][3][4][5] for both) when the fatty acyl composition of the major PE component of lens cortex is considered (Fig. 4).…”

“…Membrane-associated peptides are known to undergo intrinsic lipidation reactions by acyl transfer from membrane lipids [1]. The benchmark peptide for this process is melittin, which is lipidated in synthetic liposomes on the N-terminal amino group and on the side chains of internal lysine and, less commonly, serine residues [2,3].…”

Far from Inert: Membrane Lipids Possess Intrinsic Reactivity That Has Consequences for Cell Biology

“…Lipidation reactions have been described in most detail for the peptide melittin using liposomes as a membrane model . Other peptides are known to be reactive, including magainin II, penetratin, and PGLa . Typically, the sites to which acyl transfer occurs include the N‐terminal amino group, the ε‐amino group of lysine, and the hydroxyl group of serine.…”

“…Appealing features of this shorter pathway are its brevity and the retention of the Aβ peptide in the membrane. The timescales for a lipidation‐driven nucleation are reasonable, as even in systems with accelerated nucleation, the nucleation half times are greater than 1 h, putting them on the timescale that lipidation of melittin begins to be observable …”