New Structures and Gating of Voltage-Dependent Potassium (Kv) Channels and Their Relatives: A Multi-Domain and Dynamic Question
Voltage-dependent potassium channels (Kv channels) are crucial regulators of cell excitability that participate in a range of physiological and pathophysiological processes. These channels are molecular machines that display a mechanism (known as gating) for opening and closing a gate located in a p...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2019-01-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | http://www.mdpi.com/1422-0067/20/2/248 |
| _version_ | 1811208345557663744 |
|---|---|
| author | Francisco Barros Luis A. Pardo Pedro Domínguez Luisa Maria Sierra Pilar de la Peña |
| author_facet | Francisco Barros Luis A. Pardo Pedro Domínguez Luisa Maria Sierra Pilar de la Peña |
| author_sort | Francisco Barros |
| collection | DOAJ |
| description | Voltage-dependent potassium channels (Kv channels) are crucial regulators of cell excitability that participate in a range of physiological and pathophysiological processes. These channels are molecular machines that display a mechanism (known as gating) for opening and closing a gate located in a pore domain (PD). In Kv channels, this mechanism is triggered and controlled by changes in the magnitude of the transmembrane voltage sensed by a voltage-sensing domain (VSD). In this review, we consider several aspects of the VSD–PD coupling in Kv channels, and in some relatives, that share a common general structure characterized by a single square-shaped ion conduction pore in the center, surrounded by four VSDs located at the periphery. We compile some recent advances in the knowledge of their architecture, based in cryo-electron microscopy (cryo-EM) data for high-resolution determination of their structure, plus some new functional data obtained with channel variants in which the covalent continuity between the VSD and PD modules has been interrupted. These advances and new data bring about some reconsiderations about the use of exclusively a classical electromechanical lever model of VSD–PD coupling by some Kv channels, and open a view of the Kv-type channels as allosteric machines in which gating may be dynamically influenced by some long-range interactional/allosteric mechanisms. |
| first_indexed | 2024-04-12T04:19:35Z |
| format | Article |
| id | doaj.art-1c0a50eb20d942e6998087a2c6c685eb |
| institution | Directory Open Access Journal |
| issn | 1422-0067 |
| language | English |
| last_indexed | 2024-04-12T04:19:35Z |
| publishDate | 2019-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-1c0a50eb20d942e6998087a2c6c685eb2022-12-22T03:48:16ZengMDPI AGInternational Journal of Molecular Sciences1422-00672019-01-0120224810.3390/ijms20020248ijms20020248New Structures and Gating of Voltage-Dependent Potassium (Kv) Channels and Their Relatives: A Multi-Domain and Dynamic QuestionFrancisco Barros0Luis A. Pardo1Pedro Domínguez2Luisa Maria Sierra3Pilar de la Peña4Departamento de Bioquímica y Biología Molecular, Universidad de Oviedo, Edificio Santiago Gascón, Campus de El Cristo, 33006 Oviedo, Asturias, SpainOncophysiology Group, Max Planck Institute of Experimental Medicine, Hermann-Rein-Strasse 3, 37075 Göttingen, GermanyDepartamento de Bioquímica y Biología Molecular, Universidad de Oviedo, Edificio Santiago Gascón, Campus de El Cristo, 33006 Oviedo, Asturias, SpainDepartamento de Biología Funcional (Area de Genética), Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Universidad de Oviedo, 33006 Oviedo, Asturias, SpainDepartamento de Bioquímica y Biología Molecular, Universidad de Oviedo, Edificio Santiago Gascón, Campus de El Cristo, 33006 Oviedo, Asturias, SpainVoltage-dependent potassium channels (Kv channels) are crucial regulators of cell excitability that participate in a range of physiological and pathophysiological processes. These channels are molecular machines that display a mechanism (known as gating) for opening and closing a gate located in a pore domain (PD). In Kv channels, this mechanism is triggered and controlled by changes in the magnitude of the transmembrane voltage sensed by a voltage-sensing domain (VSD). In this review, we consider several aspects of the VSD–PD coupling in Kv channels, and in some relatives, that share a common general structure characterized by a single square-shaped ion conduction pore in the center, surrounded by four VSDs located at the periphery. We compile some recent advances in the knowledge of their architecture, based in cryo-electron microscopy (cryo-EM) data for high-resolution determination of their structure, plus some new functional data obtained with channel variants in which the covalent continuity between the VSD and PD modules has been interrupted. These advances and new data bring about some reconsiderations about the use of exclusively a classical electromechanical lever model of VSD–PD coupling by some Kv channels, and open a view of the Kv-type channels as allosteric machines in which gating may be dynamically influenced by some long-range interactional/allosteric mechanisms.http://www.mdpi.com/1422-0067/20/2/248ion channelsKv channelsstructuremolecular architecturegatingelectro-allosteric coupling |
| spellingShingle | Francisco Barros Luis A. Pardo Pedro Domínguez Luisa Maria Sierra Pilar de la Peña New Structures and Gating of Voltage-Dependent Potassium (Kv) Channels and Their Relatives: A Multi-Domain and Dynamic Question International Journal of Molecular Sciences ion channels Kv channels structure molecular architecture gating electro-allosteric coupling |
| title | New Structures and Gating of Voltage-Dependent Potassium (Kv) Channels and Their Relatives: A Multi-Domain and Dynamic Question |
| title_full | New Structures and Gating of Voltage-Dependent Potassium (Kv) Channels and Their Relatives: A Multi-Domain and Dynamic Question |
| title_fullStr | New Structures and Gating of Voltage-Dependent Potassium (Kv) Channels and Their Relatives: A Multi-Domain and Dynamic Question |
| title_full_unstemmed | New Structures and Gating of Voltage-Dependent Potassium (Kv) Channels and Their Relatives: A Multi-Domain and Dynamic Question |
| title_short | New Structures and Gating of Voltage-Dependent Potassium (Kv) Channels and Their Relatives: A Multi-Domain and Dynamic Question |
| title_sort | new structures and gating of voltage dependent potassium kv channels and their relatives a multi domain and dynamic question |
| topic | ion channels Kv channels structure molecular architecture gating electro-allosteric coupling |
| url | http://www.mdpi.com/1422-0067/20/2/248 |
| work_keys_str_mv | AT franciscobarros newstructuresandgatingofvoltagedependentpotassiumkvchannelsandtheirrelativesamultidomainanddynamicquestion AT luisapardo newstructuresandgatingofvoltagedependentpotassiumkvchannelsandtheirrelativesamultidomainanddynamicquestion AT pedrodominguez newstructuresandgatingofvoltagedependentpotassiumkvchannelsandtheirrelativesamultidomainanddynamicquestion AT luisamariasierra newstructuresandgatingofvoltagedependentpotassiumkvchannelsandtheirrelativesamultidomainanddynamicquestion AT pilardelapena newstructuresandgatingofvoltagedependentpotassiumkvchannelsandtheirrelativesamultidomainanddynamicquestion |