Breaking the hydrophobicity of the MscL pore: insights into a charge-induced gating mechanism.
The mechanosensitive channel of large conductance (MscL) is a protein that responds to membrane tension by opening a transient pore during osmotic downshock. Due to its large pore size and functional reconstitution into lipid membranes, MscL has been proposed as a promising artificial nanovalve suit...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0120196 |
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| author | Balasubramanian Chandramouli Danilo Di Maio Giordano Mancini Vincenzo Barone Giuseppe Brancato |
| author_facet | Balasubramanian Chandramouli Danilo Di Maio Giordano Mancini Vincenzo Barone Giuseppe Brancato |
| author_sort | Balasubramanian Chandramouli |
| collection | DOAJ |
| description | The mechanosensitive channel of large conductance (MscL) is a protein that responds to membrane tension by opening a transient pore during osmotic downshock. Due to its large pore size and functional reconstitution into lipid membranes, MscL has been proposed as a promising artificial nanovalve suitable for biotechnological applications. For example, site-specific mutations and tailored chemical modifications have shown how MscL channel gating can be triggered in the absence of tension by introducing charged residues at the hydrophobic pore level. Recently, engineered MscL proteins responsive to stimuli like pH or light have been reported. Inspired by experiments, we present a thorough computational study aiming at describing, with atomistic detail, the artificial gating mechanism and the molecular transport properties of a light-actuated bacterial MscL channel, in which a charge-induced gating mechanism has been enabled through the selective cleavage of photo-sensitive alkylating agents. Properties such as structural transitions, pore dimension, ion flux and selectivity have been carefully analyzed. Besides, the effects of charge on alternative sites of the channel with respect to those already reported have been addressed. Overall, our results provide useful molecular insights into the structural events accompanying the engineered MscL channel gating and the interplay of electrostatic effects, channel opening and permeation properties. In addition, we describe how the experimentally observed ionic current in a single-subunit charged MscL mutant is obtained through a hydrophobicity breaking mechanism involving an asymmetric inter-subunit motion. |
| format | Article |
| id | doaj-art-96427c102a574ce4a1d5d43d02cdfe9b |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-96427c102a574ce4a1d5d43d02cdfe9b2025-08-20T02:34:07ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01103e012019610.1371/journal.pone.0120196Breaking the hydrophobicity of the MscL pore: insights into a charge-induced gating mechanism.Balasubramanian ChandramouliDanilo Di MaioGiordano ManciniVincenzo BaroneGiuseppe BrancatoThe mechanosensitive channel of large conductance (MscL) is a protein that responds to membrane tension by opening a transient pore during osmotic downshock. Due to its large pore size and functional reconstitution into lipid membranes, MscL has been proposed as a promising artificial nanovalve suitable for biotechnological applications. For example, site-specific mutations and tailored chemical modifications have shown how MscL channel gating can be triggered in the absence of tension by introducing charged residues at the hydrophobic pore level. Recently, engineered MscL proteins responsive to stimuli like pH or light have been reported. Inspired by experiments, we present a thorough computational study aiming at describing, with atomistic detail, the artificial gating mechanism and the molecular transport properties of a light-actuated bacterial MscL channel, in which a charge-induced gating mechanism has been enabled through the selective cleavage of photo-sensitive alkylating agents. Properties such as structural transitions, pore dimension, ion flux and selectivity have been carefully analyzed. Besides, the effects of charge on alternative sites of the channel with respect to those already reported have been addressed. Overall, our results provide useful molecular insights into the structural events accompanying the engineered MscL channel gating and the interplay of electrostatic effects, channel opening and permeation properties. In addition, we describe how the experimentally observed ionic current in a single-subunit charged MscL mutant is obtained through a hydrophobicity breaking mechanism involving an asymmetric inter-subunit motion.https://doi.org/10.1371/journal.pone.0120196 |
| spellingShingle | Balasubramanian Chandramouli Danilo Di Maio Giordano Mancini Vincenzo Barone Giuseppe Brancato Breaking the hydrophobicity of the MscL pore: insights into a charge-induced gating mechanism. PLoS ONE |
| title | Breaking the hydrophobicity of the MscL pore: insights into a charge-induced gating mechanism. |
| title_full | Breaking the hydrophobicity of the MscL pore: insights into a charge-induced gating mechanism. |
| title_fullStr | Breaking the hydrophobicity of the MscL pore: insights into a charge-induced gating mechanism. |
| title_full_unstemmed | Breaking the hydrophobicity of the MscL pore: insights into a charge-induced gating mechanism. |
| title_short | Breaking the hydrophobicity of the MscL pore: insights into a charge-induced gating mechanism. |
| title_sort | breaking the hydrophobicity of the mscl pore insights into a charge induced gating mechanism |
| url | https://doi.org/10.1371/journal.pone.0120196 |
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