Dynorphin A induces membrane permeabilization by formation of proteolipidic pores. Insights from electrophysiology and computational simulations
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Other documents of the author: Perini, Deborah Aurora; Aguilella-Arzo, Marcel; Alcaraz, Antonio; Perálvarez-Marín, Alex; Queralt-Martín, María
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comunitat-uji-handle2:10234/2507
comunitat-uji-handle3:10234/6973
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Title
Dynorphin A induces membrane permeabilization by formation of proteolipidic pores. Insights from electrophysiology and computational simulationsAuthor (s)
Date
2021-12-16Publisher
ElsevierBibliographic citation
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.Type
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Abstract
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. [-]
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Computational and Structural Biotechnology Journal, Vol. 20, 2022Funder Name
Spanish Government MCIN/AEI/ 10.13039/501100011033 | Universitat Jaume I | Generalitat Valenciana
Project code
2019-108434GB-I00 | IJC2018-035283-I | 2020-120222GB-I00 | UJI-B2018-53 | UJI-A2020-21 | GRISOLIAP/2018/061 | AICO/2020/066
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© 2021 The Authors. Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology.
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