Beta-Barrel Channel Response to High Electric Fields: Functional Gating or Reversible Denaturation?
Ion channels exhibit gating behavior, fluctuating between open and closed states, with the transmembrane voltage serving as one of the essential regulators of this process. Voltage gating is a fundamental functional aspect underlying the regulation of ion-selective, mostly α-helical, channels primar...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/23/16655 |
| _version_ | 1797400144894754816 |
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| author | Ekaterina M. Nestorovich Sergey M. Bezrukov |
| author_facet | Ekaterina M. Nestorovich Sergey M. Bezrukov |
| author_sort | Ekaterina M. Nestorovich |
| collection | DOAJ |
| description | Ion channels exhibit gating behavior, fluctuating between open and closed states, with the transmembrane voltage serving as one of the essential regulators of this process. Voltage gating is a fundamental functional aspect underlying the regulation of ion-selective, mostly α-helical, channels primarily found in excitable cell membranes. In contrast, there exists another group of larger, and less selective, β-barrel channels of a different origin, which are not directly associated with cell excitability. Remarkably, these channels can also undergo closing, or “gating”, induced by sufficiently strong electric fields. Once the field is removed, the channels reopen, preserving a memory of the gating process. In this study, we explored the hypothesis that the voltage-induced closure of the β-barrel channels can be seen as a form of reversible protein denaturation by the high electric fields applied in model membranes experiments—typically exceeding twenty million volts per meter—rather than a manifestation of functional gating. Here, we focused on the bacterial outer membrane channel OmpF reconstituted into planar lipid bilayers and analyzed various characteristics of the closing-opening process that support this idea. Specifically, we considered the nearly symmetric response to voltages of both polarities, the presence of multiple closed states, the stabilization of the open conformation in channel clusters, the long-term gating memory, and the Hofmeister effects in closing kinetics. Furthermore, we contemplate the evolutionary aspect of the phenomenon, proposing that the field-induced denaturation of membrane proteins might have served as a starting point for their development into amazing molecular machines such as voltage-gated channels of nerve and muscle cells. |
| first_indexed | 2024-03-09T01:51:17Z |
| format | Article |
| id | doaj.art-d9a8d56389024eb1b28961afec324843 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T01:51:17Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-d9a8d56389024eb1b28961afec3248432023-12-08T15:16:40ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-11-0124231665510.3390/ijms242316655Beta-Barrel Channel Response to High Electric Fields: Functional Gating or Reversible Denaturation?Ekaterina M. Nestorovich0Sergey M. Bezrukov1Department of Biology, The Catholic University of America, Washington, DC 20064, USASection on Molecular Transport, <i>Eunice Kennedy Shriver</i> National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USAIon channels exhibit gating behavior, fluctuating between open and closed states, with the transmembrane voltage serving as one of the essential regulators of this process. Voltage gating is a fundamental functional aspect underlying the regulation of ion-selective, mostly α-helical, channels primarily found in excitable cell membranes. In contrast, there exists another group of larger, and less selective, β-barrel channels of a different origin, which are not directly associated with cell excitability. Remarkably, these channels can also undergo closing, or “gating”, induced by sufficiently strong electric fields. Once the field is removed, the channels reopen, preserving a memory of the gating process. In this study, we explored the hypothesis that the voltage-induced closure of the β-barrel channels can be seen as a form of reversible protein denaturation by the high electric fields applied in model membranes experiments—typically exceeding twenty million volts per meter—rather than a manifestation of functional gating. Here, we focused on the bacterial outer membrane channel OmpF reconstituted into planar lipid bilayers and analyzed various characteristics of the closing-opening process that support this idea. Specifically, we considered the nearly symmetric response to voltages of both polarities, the presence of multiple closed states, the stabilization of the open conformation in channel clusters, the long-term gating memory, and the Hofmeister effects in closing kinetics. Furthermore, we contemplate the evolutionary aspect of the phenomenon, proposing that the field-induced denaturation of membrane proteins might have served as a starting point for their development into amazing molecular machines such as voltage-gated channels of nerve and muscle cells.https://www.mdpi.com/1422-0067/24/23/16655protein foldingsingle-molecule experimentschannel reconstitutionhysteresisHofmeister series |
| spellingShingle | Ekaterina M. Nestorovich Sergey M. Bezrukov Beta-Barrel Channel Response to High Electric Fields: Functional Gating or Reversible Denaturation? International Journal of Molecular Sciences protein folding single-molecule experiments channel reconstitution hysteresis Hofmeister series |
| title | Beta-Barrel Channel Response to High Electric Fields: Functional Gating or Reversible Denaturation? |
| title_full | Beta-Barrel Channel Response to High Electric Fields: Functional Gating or Reversible Denaturation? |
| title_fullStr | Beta-Barrel Channel Response to High Electric Fields: Functional Gating or Reversible Denaturation? |
| title_full_unstemmed | Beta-Barrel Channel Response to High Electric Fields: Functional Gating or Reversible Denaturation? |
| title_short | Beta-Barrel Channel Response to High Electric Fields: Functional Gating or Reversible Denaturation? |
| title_sort | beta barrel channel response to high electric fields functional gating or reversible denaturation |
| topic | protein folding single-molecule experiments channel reconstitution hysteresis Hofmeister series |
| url | https://www.mdpi.com/1422-0067/24/23/16655 |
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