Structural properties of PAS domains from the KCNH potassium channels.
KCNH channels form an important family of voltage gated potassium channels. These channels include a N-terminal Per-Arnt-Sim (PAS) domain with unknown function. In other proteins PAS domains are implicated in cellular responses to environmental queues through small molecule binding or involvement in...
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0059265&type=printable |
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| author | Ricardo Adaixo Carol A Harley Artur F Castro-Rodrigues João H Morais-Cabral |
| author_facet | Ricardo Adaixo Carol A Harley Artur F Castro-Rodrigues João H Morais-Cabral |
| author_sort | Ricardo Adaixo |
| collection | DOAJ |
| description | KCNH channels form an important family of voltage gated potassium channels. These channels include a N-terminal Per-Arnt-Sim (PAS) domain with unknown function. In other proteins PAS domains are implicated in cellular responses to environmental queues through small molecule binding or involvement in signaling cascades. To better understand their role we characterized the structural properties of several channel PAS domains. We determined high resolution structures of PAS domains from the mouse EAG (mEAG), drosophila ELK (dELK) and human ERG (hERG) channels and also of the hERG domain without the first nine amino acids. We analyzed these structures for features connected to ligand binding and signaling in other PAS domains. In particular, we have found cavities in the hERG and mEAG structures that share similarities with the ligand binding sites from other PAS domains. These cavities are lined by polar and apolar chemical groups and display potential flexibility in their volume. We have also found that the hydrophobic patch on the domain β-sheet is a conserved feature and appears to drive the formation of protein-protein contacts. In addition, the structures of the dELK domain and of the truncated hERG domain revealed the presence of N-terminal helices. These helices are equivalent to the helix described in the hERG NMR structures and are known to be important for channel function. Overall, these channel domains retain many of the PAS domain characteristics known to be important for cell signaling. |
| format | Article |
| id | doaj-art-e38e44c2b7d840378f816e0b0e93d0d8 |
| institution | DOAJ |
| issn | 1932-6203 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-e38e44c2b7d840378f816e0b0e93d0d82025-08-20T03:00:55ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0183e5926510.1371/journal.pone.0059265Structural properties of PAS domains from the KCNH potassium channels.Ricardo AdaixoCarol A HarleyArtur F Castro-RodriguesJoão H Morais-CabralKCNH channels form an important family of voltage gated potassium channels. These channels include a N-terminal Per-Arnt-Sim (PAS) domain with unknown function. In other proteins PAS domains are implicated in cellular responses to environmental queues through small molecule binding or involvement in signaling cascades. To better understand their role we characterized the structural properties of several channel PAS domains. We determined high resolution structures of PAS domains from the mouse EAG (mEAG), drosophila ELK (dELK) and human ERG (hERG) channels and also of the hERG domain without the first nine amino acids. We analyzed these structures for features connected to ligand binding and signaling in other PAS domains. In particular, we have found cavities in the hERG and mEAG structures that share similarities with the ligand binding sites from other PAS domains. These cavities are lined by polar and apolar chemical groups and display potential flexibility in their volume. We have also found that the hydrophobic patch on the domain β-sheet is a conserved feature and appears to drive the formation of protein-protein contacts. In addition, the structures of the dELK domain and of the truncated hERG domain revealed the presence of N-terminal helices. These helices are equivalent to the helix described in the hERG NMR structures and are known to be important for channel function. Overall, these channel domains retain many of the PAS domain characteristics known to be important for cell signaling.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0059265&type=printable |
| spellingShingle | Ricardo Adaixo Carol A Harley Artur F Castro-Rodrigues João H Morais-Cabral Structural properties of PAS domains from the KCNH potassium channels. PLoS ONE |
| title | Structural properties of PAS domains from the KCNH potassium channels. |
| title_full | Structural properties of PAS domains from the KCNH potassium channels. |
| title_fullStr | Structural properties of PAS domains from the KCNH potassium channels. |
| title_full_unstemmed | Structural properties of PAS domains from the KCNH potassium channels. |
| title_short | Structural properties of PAS domains from the KCNH potassium channels. |
| title_sort | structural properties of pas domains from the kcnh potassium channels |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0059265&type=printable |
| work_keys_str_mv | AT ricardoadaixo structuralpropertiesofpasdomainsfromthekcnhpotassiumchannels AT carolaharley structuralpropertiesofpasdomainsfromthekcnhpotassiumchannels AT arturfcastrorodrigues structuralpropertiesofpasdomainsfromthekcnhpotassiumchannels AT joaohmoraiscabral structuralpropertiesofpasdomainsfromthekcnhpotassiumchannels |