The influenza A Virus M2 channel: a molecular modeling and simulation study
The M2 protein of influenza virus forms ion channels activated by low pH which are proton permeable and play a key role in the life cycle of the virus. M2 is a 97-residue integral membrane protein containing a single transmembrane (TM) helix. M2 is present as disulfide-linked homotetramers. The TM d...
| Main Authors: | , , , |
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| Format: | Journal article |
| Language: | English |
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Elsevier
1997
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| _version_ | 1797097511551238144 |
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| author | Sansom, M Kerr, I Smith, G Son, H |
| author_facet | Sansom, M Kerr, I Smith, G Son, H |
| author_sort | Sansom, M |
| collection | OXFORD |
| description | The M2 protein of influenza virus forms ion channels activated by low pH which are proton permeable and play a key role in the life cycle of the virus. M2 is a 97-residue integral membrane protein containing a single transmembrane (TM) helix. M2 is present as disulfide-linked homotetramers. The TM domain of M2 has been modeled as a bundle of four parallel M2 helices. The helix bundle forms a left-handed supercoil surrounding a central pore. Residue H37 has been implicated in the mechanism of low-pH activation of the channel. Models generated with H37 in a fully deprotonated state exhibit a pore occluded by a ring of H37 side chains oriented toward the lumen of the pore. Models with H37 in a fully protonated state no longer exhibit such occlusion of the pore, as the H37 side chains adopt a more interfacial location. Extended molecular dynamics simulations with water molecules within and at the mouths of the pores support this distinction between the H37-deprotonated and H37-protonated models. These simulations suggest that only in the H37-protonated model is there a continuous column of water extending the entire length of the central pore. A mechanism for activation of M2 by low pH is presented in which the H37-deprotonated model corresponds to the “closed” form of the channel, while the H37-protonated model corresponds to the “open” form. A switch from the closed to the open form of the channel occurs if H37 is protonated midway through a simulation. The open channel is suggested to contain a wire of H-bonded water molecules which enables proton permeability. |
| first_indexed | 2024-03-07T04:56:35Z |
| format | Journal article |
| id | oxford-uuid:d6ceccde-ea95-499b-ba96-474025e56bd6 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T04:56:35Z |
| publishDate | 1997 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | oxford-uuid:d6ceccde-ea95-499b-ba96-474025e56bd62022-03-27T08:36:19ZThe influenza A Virus M2 channel: a molecular modeling and simulation studyJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:d6ceccde-ea95-499b-ba96-474025e56bd6VirusesGenetics (medical sciences)EnglishOxford University Research Archive - ValetElsevier1997Sansom, MKerr, ISmith, GSon, HThe M2 protein of influenza virus forms ion channels activated by low pH which are proton permeable and play a key role in the life cycle of the virus. M2 is a 97-residue integral membrane protein containing a single transmembrane (TM) helix. M2 is present as disulfide-linked homotetramers. The TM domain of M2 has been modeled as a bundle of four parallel M2 helices. The helix bundle forms a left-handed supercoil surrounding a central pore. Residue H37 has been implicated in the mechanism of low-pH activation of the channel. Models generated with H37 in a fully deprotonated state exhibit a pore occluded by a ring of H37 side chains oriented toward the lumen of the pore. Models with H37 in a fully protonated state no longer exhibit such occlusion of the pore, as the H37 side chains adopt a more interfacial location. Extended molecular dynamics simulations with water molecules within and at the mouths of the pores support this distinction between the H37-deprotonated and H37-protonated models. These simulations suggest that only in the H37-protonated model is there a continuous column of water extending the entire length of the central pore. A mechanism for activation of M2 by low pH is presented in which the H37-deprotonated model corresponds to the “closed” form of the channel, while the H37-protonated model corresponds to the “open” form. A switch from the closed to the open form of the channel occurs if H37 is protonated midway through a simulation. The open channel is suggested to contain a wire of H-bonded water molecules which enables proton permeability. |
| spellingShingle | Viruses Genetics (medical sciences) Sansom, M Kerr, I Smith, G Son, H The influenza A Virus M2 channel: a molecular modeling and simulation study |
| title | The influenza A Virus M2 channel: a molecular modeling and simulation study |
| title_full | The influenza A Virus M2 channel: a molecular modeling and simulation study |
| title_fullStr | The influenza A Virus M2 channel: a molecular modeling and simulation study |
| title_full_unstemmed | The influenza A Virus M2 channel: a molecular modeling and simulation study |
| title_short | The influenza A Virus M2 channel: a molecular modeling and simulation study |
| title_sort | influenza a virus m2 channel a molecular modeling and simulation study |
| topic | Viruses Genetics (medical sciences) |
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