Structure and Dynamics of Cinnamycin-Lipid Complexes: Mechanisms of Selectivity for Phosphatidylethanolamine Lipids.

Autor:	Vestergaard M; Center for Insoluble Protein Structures (inSPIN), Interdisciplinary Nanoscience Center (iNANO), Department of Chemistry, Aarhus University, Langelandsgade 140, DK-8000 Aarhus C, Denmark., Berglund NA; Center for Insoluble Protein Structures (inSPIN), Interdisciplinary Nanoscience Center (iNANO), Department of Chemistry, Aarhus University, Langelandsgade 140, DK-8000 Aarhus C, Denmark., Hsu PC; Center for Insoluble Protein Structures (inSPIN), Interdisciplinary Nanoscience Center (iNANO), Department of Chemistry, Aarhus University, Langelandsgade 140, DK-8000 Aarhus C, Denmark., Song C; Department of Biochemistry, University of Oxford, South Parks Road, OX1 3QU Oxford, United Kingdom., Koldsø H; Department of Biochemistry, University of Oxford, South Parks Road, OX1 3QU Oxford, United Kingdom., Schiøtt B; Center for Insoluble Protein Structures (inSPIN), Interdisciplinary Nanoscience Center (iNANO), Department of Chemistry, Aarhus University, Langelandsgade 140, DK-8000 Aarhus C, Denmark., Sansom MSP; Department of Biochemistry, University of Oxford, South Parks Road, OX1 3QU Oxford, United Kingdom.
Jazyk:	angličtina
Zdroj:	ACS omega [ACS Omega] 2019 Oct 28; Vol. 4 (20), pp. 18889-18899. Date of Electronic Publication: 2019 Oct 28 (Print Publication: 2019).
DOI:	10.1021/acsomega.9b02949
Abstrakt:	Cinnamycin is a lantibiotic peptide, which selectively binds to and permeabilizes membranes containing phosphatidylethanolamine (PE) lipids. As PE is a major component of many bacterial cell membranes, cinnamycin has considerable potential for destroying these. In this study, molecular dynamics simulations are used to elucidate the structure of a lipid-cinnamycin complex and the origin of selective lipid binding. The simulations reveal that cinnamycin selectively binds to PE by forming an extensive hydrogen-bonding network involving all three hydrogen atoms of the primary ammonium group of the PE head group. The substitution of a single hydrogen atom with a methyl group on the ammonium nitrogen destabilizes this hydrogen-bonding network. In addition to binding the primary ammonium group, cinnamycin also interacts with the phosphate group of the lipid through a previously uncharacterized phosphate-binding site formed by the backbone Phe10-Abu11-Phe12-Val13 moieties (Abu = 1-α-aminobutyric acid). In addition, hydroxylation of Asp15 at Cβ plays a role in selective binding of PE due to its tight interaction with the charged amine of the lipid head group. The simulations reveal that the position and orientation of the peptide in the membrane depend on the type of lipid to which it binds, suggesting a reason for why cinnamycin selectively permeabilizes PE-containing membranes. Competing Interests: The authors declare no competing financial interest. (Copyright © 2019 American Chemical Society.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu