Non-equivalent role of TM2 gating hinges in heteromeric Kir4.1/Kir5.1 potassium channels.
Comparison of the crystal structures of the KcsA and MthK potassium channels suggests that the process of opening a K(+) channel involves pivoted bending of the inner pore-lining helices at a highly conserved glycine residue. This bending motion is proposed to splay the transmembrane domains outward...
| Main Authors: | , |
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| Format: | Journal article |
| Language: | English |
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2008
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| _version_ | 1826266932867760128 |
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| author | Shang, L Tucker, S |
| author_facet | Shang, L Tucker, S |
| author_sort | Shang, L |
| collection | OXFORD |
| description | Comparison of the crystal structures of the KcsA and MthK potassium channels suggests that the process of opening a K(+) channel involves pivoted bending of the inner pore-lining helices at a highly conserved glycine residue. This bending motion is proposed to splay the transmembrane domains outwards to widen the gate at the "helix-bundle crossing". However, in the inwardly rectifying (Kir) potassium channel family, the role of this "hinge" residue in the second transmembrane domain (TM2) and that of another putative glycine gating hinge at the base of TM2 remain controversial. We investigated the role of these two positions in heteromeric Kir4.1/Kir5.1 channels, which are unique amongst Kir channels in that both subunits lack a conserved glycine at the upper hinge position. Contrary to the effect seen in other channels, increasing the potential flexibility of TM2 by glycine substitutions at the upper hinge position decreases channel opening. Furthermore, the contribution of the Kir4.1 subunit to this process is dominant compared to Kir5.1, demonstrating a non-equivalent contribution of these two subunits to the gating process. A homology model of heteromeric Kir4.1/Kir5.1 shows that these upper "hinge" residues are in close contact with the base of the pore alpha-helix that supports the selectivity filter. Our results also indicate that the highly conserved glycine at the "lower" gating hinge position is required for tight packing of the TM2 helices at the helix-bundle crossing, rather than acting as a hinge residue. |
| first_indexed | 2024-03-06T20:46:27Z |
| format | Journal article |
| id | oxford-uuid:3615ab5f-f28b-4f37-80db-f3ec436509da |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T20:46:27Z |
| publishDate | 2008 |
| record_format | dspace |
| spelling | oxford-uuid:3615ab5f-f28b-4f37-80db-f3ec436509da2022-03-26T13:35:37ZNon-equivalent role of TM2 gating hinges in heteromeric Kir4.1/Kir5.1 potassium channels.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:3615ab5f-f28b-4f37-80db-f3ec436509daEnglishSymplectic Elements at Oxford2008Shang, LTucker, SComparison of the crystal structures of the KcsA and MthK potassium channels suggests that the process of opening a K(+) channel involves pivoted bending of the inner pore-lining helices at a highly conserved glycine residue. This bending motion is proposed to splay the transmembrane domains outwards to widen the gate at the "helix-bundle crossing". However, in the inwardly rectifying (Kir) potassium channel family, the role of this "hinge" residue in the second transmembrane domain (TM2) and that of another putative glycine gating hinge at the base of TM2 remain controversial. We investigated the role of these two positions in heteromeric Kir4.1/Kir5.1 channels, which are unique amongst Kir channels in that both subunits lack a conserved glycine at the upper hinge position. Contrary to the effect seen in other channels, increasing the potential flexibility of TM2 by glycine substitutions at the upper hinge position decreases channel opening. Furthermore, the contribution of the Kir4.1 subunit to this process is dominant compared to Kir5.1, demonstrating a non-equivalent contribution of these two subunits to the gating process. A homology model of heteromeric Kir4.1/Kir5.1 shows that these upper "hinge" residues are in close contact with the base of the pore alpha-helix that supports the selectivity filter. Our results also indicate that the highly conserved glycine at the "lower" gating hinge position is required for tight packing of the TM2 helices at the helix-bundle crossing, rather than acting as a hinge residue. |
| spellingShingle | Shang, L Tucker, S Non-equivalent role of TM2 gating hinges in heteromeric Kir4.1/Kir5.1 potassium channels. |
| title | Non-equivalent role of TM2 gating hinges in heteromeric Kir4.1/Kir5.1 potassium channels. |
| title_full | Non-equivalent role of TM2 gating hinges in heteromeric Kir4.1/Kir5.1 potassium channels. |
| title_fullStr | Non-equivalent role of TM2 gating hinges in heteromeric Kir4.1/Kir5.1 potassium channels. |
| title_full_unstemmed | Non-equivalent role of TM2 gating hinges in heteromeric Kir4.1/Kir5.1 potassium channels. |
| title_short | Non-equivalent role of TM2 gating hinges in heteromeric Kir4.1/Kir5.1 potassium channels. |
| title_sort | non equivalent role of tm2 gating hinges in heteromeric kir4 1 kir5 1 potassium channels |
| work_keys_str_mv | AT shangl nonequivalentroleoftm2gatinghingesinheteromerickir41kir51potassiumchannels AT tuckers nonequivalentroleoftm2gatinghingesinheteromerickir41kir51potassiumchannels |