Influence of lipids on the hydrophobic barrier within the pore of the TWIK-1 K2P channel
Several recent ion channel structures have revealed large side portals, or ‘fenestrations’ at the interface between their transmembrane helices that potentially expose the ion conduction pathway to the lipid core of the bilayer. In a recent study we demonstrated that functional activity of the TWIK-...
| Main Authors: | , , , , |
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| Format: | Journal article |
| Language: | English |
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Taylor and Francis
2014
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| _version_ | 1797063260551249920 |
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| author | Aryal, P Abd-Wahab, F Bucci, G Sansom, M Tucker, S Bucci, G |
| author_facet | Aryal, P Abd-Wahab, F Bucci, G Sansom, M Tucker, S Bucci, G |
| author_sort | Aryal, P |
| collection | OXFORD |
| description | Several recent ion channel structures have revealed large side portals, or ‘fenestrations’ at the interface between their transmembrane helices that potentially expose the ion conduction pathway to the lipid core of the bilayer. In a recent study we demonstrated that functional activity of the TWIK-1 K2P channel is influenced by the presence of hydrophobic residues deep within the inner pore. These residues are located near the fenestrations in the TWIK-1 structure and promote dewetting of the pore by forming a hydrophobic barrier to ion conduction. During our previous MD simulations, lipid tails were observed to enter these fenestrations. In this addendum to that study, we investigate lipid contribution to the dewetting process. Our results demonstrate that lipid tails from both the upper and lower leaflets occupy the fenestrations and penetrate into the pore. The lipid tails do not sterically occlude the pore, but there is an inverse correlation between the presence of water within the hydrophobic barrier and the number of lipids tails within the lining of the pore. However, dewetting still occurs in the absence of lipids tails, and pore hydration appears to be determined primarily by those side-chains lining the narrowest part of the pore cavity. |
| first_indexed | 2024-03-06T20:57:17Z |
| format | Journal article |
| id | oxford-uuid:39b00288-a5fc-41a2-8187-7952a0c43fc1 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T20:57:17Z |
| publishDate | 2014 |
| publisher | Taylor and Francis |
| record_format | dspace |
| spelling | oxford-uuid:39b00288-a5fc-41a2-8187-7952a0c43fc12022-03-26T13:57:03ZInfluence of lipids on the hydrophobic barrier within the pore of the TWIK-1 K2P channelJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:39b00288-a5fc-41a2-8187-7952a0c43fc1EnglishSymplectic Elements at OxfordTaylor and Francis2014Aryal, PAbd-Wahab, FBucci, GSansom, MTucker, SBucci, GSeveral recent ion channel structures have revealed large side portals, or ‘fenestrations’ at the interface between their transmembrane helices that potentially expose the ion conduction pathway to the lipid core of the bilayer. In a recent study we demonstrated that functional activity of the TWIK-1 K2P channel is influenced by the presence of hydrophobic residues deep within the inner pore. These residues are located near the fenestrations in the TWIK-1 structure and promote dewetting of the pore by forming a hydrophobic barrier to ion conduction. During our previous MD simulations, lipid tails were observed to enter these fenestrations. In this addendum to that study, we investigate lipid contribution to the dewetting process. Our results demonstrate that lipid tails from both the upper and lower leaflets occupy the fenestrations and penetrate into the pore. The lipid tails do not sterically occlude the pore, but there is an inverse correlation between the presence of water within the hydrophobic barrier and the number of lipids tails within the lining of the pore. However, dewetting still occurs in the absence of lipids tails, and pore hydration appears to be determined primarily by those side-chains lining the narrowest part of the pore cavity. |
| spellingShingle | Aryal, P Abd-Wahab, F Bucci, G Sansom, M Tucker, S Bucci, G Influence of lipids on the hydrophobic barrier within the pore of the TWIK-1 K2P channel |
| title | Influence of lipids on the hydrophobic barrier within the pore of the TWIK-1 K2P channel |
| title_full | Influence of lipids on the hydrophobic barrier within the pore of the TWIK-1 K2P channel |
| title_fullStr | Influence of lipids on the hydrophobic barrier within the pore of the TWIK-1 K2P channel |
| title_full_unstemmed | Influence of lipids on the hydrophobic barrier within the pore of the TWIK-1 K2P channel |
| title_short | Influence of lipids on the hydrophobic barrier within the pore of the TWIK-1 K2P channel |
| title_sort | influence of lipids on the hydrophobic barrier within the pore of the twik 1 k2p channel |
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