Dynorphin A induces membrane permeabilization by formation of proteolipidic pores. Insights from electrophysiology and computational simulations
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Otros documentos de la autoría: Perini, Deborah Aurora; Aguilella-Arzo, Marcel; Alcaraz, Antonio; Perálvarez-Marín, Alex; Queralt-Martín, María
Metadatos
Mostrar el registro completo del ítemcomunitat-uji-handle:10234/9
comunitat-uji-handle2:10234/2507
comunitat-uji-handle3:10234/6973
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Título
Dynorphin A induces membrane permeabilization by formation of proteolipidic pores. Insights from electrophysiology and computational simulationsAutoría
Fecha de publicación
2021-12-16Editor
ElsevierCita bibliográfica
PERINI, D. Aurora, et al. Dynorphin A induces membrane permeabilization by formation of proteolipidic pores. Insights from electrophysiology and computational simulations. Computational and structural biotechnology journal, 2022, vol. 20, p. 230-240.Tipo de documento
info:eu-repo/semantics/articleVersión
info:eu-repo/semantics/publishedVersionPalabras clave / Materias
Resumen
Dynorphins are endogenous neuropeptides that function as ligands for the κ-opioid receptor. In addition to opioid activity, dynorphins can induce several pathological effects such as neurological dysfunctions and cell ... [+]
Dynorphins are endogenous neuropeptides that function as ligands for the κ-opioid receptor. In addition to opioid activity, dynorphins can induce several pathological effects such as neurological dysfunctions and cell death. Previous studies have suggested that Dynorphin A (DynA) mediates some pathogenic actions through formation of transient pores in lipid domains of the plasma membrane. Here, we use planar bilayer electrophysiology to show that DynA induces pore formation in negatively charged membranes. We find a large variability in pore conformations showing equilibrium conductance fluctuations, what disregards electroporation as the dominant mechanism of pore formation. Ion selectivity measurements showing cationic selectivity indicate that positive protein charges of DynA are stabilized by phosphatidyl serine negative charges in the formation of combined structures. We complement our study with computational simulations that assess the stability of diverse peptide arrangements in the hydrophobic core of the bilayer. We show that DynA is capable of assembling in charged membranes to form water-filled pores that conduct ions. [-]
Publicado en
Computational and Structural Biotechnology Journal, Vol. 20, 2022Entidad financiadora
Spanish Government MCIN/AEI/ 10.13039/501100011033 | Universitat Jaume I | Generalitat Valenciana
Código del proyecto o subvención
2019-108434GB-I00 | IJC2018-035283-I | 2020-120222GB-I00 | UJI-B2018-53 | UJI-A2020-21 | GRISOLIAP/2018/061 | AICO/2020/066
Derechos de acceso
© 2021 The Authors. Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology.
info:eu-repo/semantics/openAccess
info:eu-repo/semantics/openAccess
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