The lipid mediator lysophosphatidic acid induces folding of disordered peptides with basic amphipathic character into rare conformations

Abstract Membrane-active, basic amphipathic peptides represent a class of biomolecules with diverse functions. Sequentially close protein segments also show similar behaviour in several ways. Here we investigated the effect of the lipid mediator lysophosphatidic acid (LPA) on the conformation of str...

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Autores principales:	Tünde Juhász, Judith Mihály, Gergely Kohut, Csaba Németh, Károly Liliom, Tamás Beke-Somfai
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Lipid Mediator LPA Antimicrobial Peptides (AMPs) Lipid Clusters IQ Gap Protein GAP43 Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8c6990081a984eeba74d4c046588fd0a
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spelling	oai:doaj.org-article:8c6990081a984eeba74d4c046588fd0a2021-12-02T15:08:14ZThe lipid mediator lysophosphatidic acid induces folding of disordered peptides with basic amphipathic character into rare conformations10.1038/s41598-018-32786-42045-2322https://doaj.org/article/8c6990081a984eeba74d4c046588fd0a2018-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-32786-4https://doaj.org/toc/2045-2322Abstract Membrane-active, basic amphipathic peptides represent a class of biomolecules with diverse functions. Sequentially close protein segments also show similar behaviour in several ways. Here we investigated the effect of the lipid mediator lysophosphatidic acid (LPA) on the conformation of structurally disordered peptides including extracellular antimicrobial peptides (AMPs), and calmodulin-binding motifs derived from cytosolic and membrane target proteins. The interaction with associated LPA resulted in gain of ordered secondary structure elements, which for most cases were previously uncharacteristic of the particular peptide. Results revealed mechanism of the LPA-peptide interactions with regulation of the lipid on peptide conformation and oligomerization in a concentration-dependent manner involving (1) relocation of tryptophan residues into the lipid cluster, (2) multiple contacts between the binding partners dictated by complex driving forces, (3) multiple peptide binding to LPA associates with an affinity in the low micromolar range, and (4) selectivity for LPA compared with structurally related lipids. In line with recent findings showing endogenous molecules inducing structural changes in AMPs, we propose that accumulation of LPA in signalling or pathological processes might modulate host-defense activity or trigger certain processes by direct interaction with cationic amphipathic peptide sequences.Tünde JuhászJudith MihályGergely KohutCsaba NémethKároly LiliomTamás Beke-SomfaiNature PortfolioarticleLipid Mediator LPAAntimicrobial Peptides (AMPs)Lipid ClustersIQ GapProtein GAP43MedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-15 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Lipid Mediator LPA Antimicrobial Peptides (AMPs) Lipid Clusters IQ Gap Protein GAP43 Medicine R Science Q
spellingShingle	Lipid Mediator LPA Antimicrobial Peptides (AMPs) Lipid Clusters IQ Gap Protein GAP43 Medicine R Science Q Tünde Juhász Judith Mihály Gergely Kohut Csaba Németh Károly Liliom Tamás Beke-Somfai The lipid mediator lysophosphatidic acid induces folding of disordered peptides with basic amphipathic character into rare conformations
description	Abstract Membrane-active, basic amphipathic peptides represent a class of biomolecules with diverse functions. Sequentially close protein segments also show similar behaviour in several ways. Here we investigated the effect of the lipid mediator lysophosphatidic acid (LPA) on the conformation of structurally disordered peptides including extracellular antimicrobial peptides (AMPs), and calmodulin-binding motifs derived from cytosolic and membrane target proteins. The interaction with associated LPA resulted in gain of ordered secondary structure elements, which for most cases were previously uncharacteristic of the particular peptide. Results revealed mechanism of the LPA-peptide interactions with regulation of the lipid on peptide conformation and oligomerization in a concentration-dependent manner involving (1) relocation of tryptophan residues into the lipid cluster, (2) multiple contacts between the binding partners dictated by complex driving forces, (3) multiple peptide binding to LPA associates with an affinity in the low micromolar range, and (4) selectivity for LPA compared with structurally related lipids. In line with recent findings showing endogenous molecules inducing structural changes in AMPs, we propose that accumulation of LPA in signalling or pathological processes might modulate host-defense activity or trigger certain processes by direct interaction with cationic amphipathic peptide sequences.
format	article
author	Tünde Juhász Judith Mihály Gergely Kohut Csaba Németh Károly Liliom Tamás Beke-Somfai
author_facet	Tünde Juhász Judith Mihály Gergely Kohut Csaba Németh Károly Liliom Tamás Beke-Somfai
author_sort	Tünde Juhász
title	The lipid mediator lysophosphatidic acid induces folding of disordered peptides with basic amphipathic character into rare conformations
title_short	The lipid mediator lysophosphatidic acid induces folding of disordered peptides with basic amphipathic character into rare conformations
title_full	The lipid mediator lysophosphatidic acid induces folding of disordered peptides with basic amphipathic character into rare conformations
title_fullStr	The lipid mediator lysophosphatidic acid induces folding of disordered peptides with basic amphipathic character into rare conformations
title_full_unstemmed	The lipid mediator lysophosphatidic acid induces folding of disordered peptides with basic amphipathic character into rare conformations
title_sort	lipid mediator lysophosphatidic acid induces folding of disordered peptides with basic amphipathic character into rare conformations
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/8c6990081a984eeba74d4c046588fd0a
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The lipid mediator lysophosphatidic acid induces folding of disordered peptides with basic amphipathic character into rare conformations

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