Nonpolar interactions between trans-membrane helical EGF peptide and phosphatidylcholines, sphingomyelins and cholesterol. Molecular dynamics simulation studies

T. Róg, K. Murzyn, M.E.J. Karttunen, M. Pasenkiewicz-Gierula

    Onderzoeksoutput: Bijdrage aan tijdschriftTijdschriftartikelAcademicpeer review

    12 Citaten (Scopus)

    Samenvatting

    A molecular dynamics simulation study of four lipid bilayers with inserted trans-membrane helical fragment of epithelial growth factor (EGF) receptor (EGF peptide) was performed. The lipid bilayers differ in their lipid composition and consist of (i) unsaturated phosphatidylcholine (palmitoyloleoylphosphatidylcholine, POPC), (ii) POPC and 20 mol% of cholesterol (Chol), (iii) sphingomyelin (SM) and 20 mol% of Chol, and (iv) SM and 50 mol% of Chol. Only 1 out of 26 residues in the EGF-peptide sequence is polar (Thr). The hydrophobic thickness of each bilayer is different but shorter than the length of the peptide and so, due to hydrophobic mismatch, the inserted peptide is tilted in each bilayer. Additionally, in the POPC bilayer, which is the thinnest, the peptide loses its helical structure in a short three-amino acid fragment. This facilitates bending of the peptide and burying all hydrophobic amino acids inside the membrane core (Figure 1(b)). Bilayer lipid composition affects interactions between the peptide and lipids in the membrane core. Chol increases packing of atoms relative to the peptide side chains, and thus increases van der Waals interactions. On average, the packing around the peptide is higher in SM-based bilayers than POPC-based bilayers but for certain amino acids, packing depends on their position relative to the bilayer center. In the bilayer center, packing is higher in POPC-based bilayers, while in regions closer to the interface packing is higher in SM-based bilayers. In general, amino acids with larger side chains interact strongly with lipids, and thus the peptide sequence is important for the pattern of interactions at different membrane depths. This pattern closely resembles the shape of recently published lateral pressure profiles [Ollila et alJ. Struct. Biol. DOI:10.1016/j.jsb.2007.01.012]. Keywords: membrane heterogeneity;lipid rafts;hydrophobic mismatch;van der Waals interactions;membrane packing;EGF receptor
    Originele taal-2Engels
    Pagina's (van-tot)374-382
    TijdschriftJournal of Peptide Science
    Volume14
    Nummer van het tijdschrift4
    DOI's
    StatusGepubliceerd - 2008

    Vingerafdruk

    Duik in de onderzoeksthema's van 'Nonpolar interactions between trans-membrane helical EGF peptide and phosphatidylcholines, sphingomyelins and cholesterol. Molecular dynamics simulation studies'. Samen vormen ze een unieke vingerafdruk.

    Citeer dit