M2 Proton Channel: Difference between revisions
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== Central Cavity == | == Central Cavity == | ||
The hydrophilic residues in each α-helix monomer are oriented towards the pore lumen.<ref name="Wu" /> The <scene name='User:Sarah_Henke/Sandbox_1/Hydrophobic/1'>hydrophobic</scene> residues will be in contact with the membrane (Color code= {{Template:ColorKey_Hydrophobic}} or {{Template:ColorKey_Polar}}). Most of the residues in the M2 channel are hydrophobic except Ser31 Gly34, and His37.<ref name="Wu" /> The central cavity of the M2 proton channel is most constricted near residue Val27. After this residue, the cavity opens to a water-filled pore that is lined with residues Ala30, Ser31, and Gly34.<ref name="Stouffer" /> Mutagenesis studies have found that the residues facing the pore are Val27, Ala30, Ser31, Gly34, His37, Leu38, and Trp41.<ref name="Wu" /> The central cavity also constricts at residues His37 and Trp41.<ref name="Stouffer" /> Residues <scene name='User:Sarah_Henke/Sandbox_1/His_37/1'>His37</scene> and <scene name='User:Sarah_Henke/Sandbox_1/Trp20/1'>Trp41</scene> play a key role in the gating mechanism.<ref name="Wu" /> In the closed state, the His37 and Trp41 residues block the channel, preventing proton conductance. <ref name="Lear">PMID:12972146 </ref> | The hydrophilic residues in each α-helix monomer are oriented towards the pore lumen.<ref name="Wu" /> The <scene name='User:Sarah_Henke/Sandbox_1/Hydrophobic/1'>hydrophobic</scene> residues will be in contact with the membrane (Color code= {{Template:ColorKey_Hydrophobic}} or {{Template:ColorKey_Polar}}). Most of the residues in the M2 channel are hydrophobic except Ser31 Gly34, and His37.<ref name="Wu" /> The central cavity of the M2 proton channel is most constricted near residue Val27. After this residue, the cavity opens to a water-filled pore that is lined with residues Ala30, Ser31, and Gly34.<ref name="Stouffer" /> Mutagenesis studies have found that the residues facing the pore are Val27, Ala30, Ser31, Gly34, His37, Leu38, and Trp41.<ref name="Wu" /> The central cavity also constricts at residues His37 and Trp41.<ref name="Stouffer" /> Residues <scene name='User:Sarah_Henke/Sandbox_1/His_37/1'>His37</scene> and <scene name='User:Sarah_Henke/Sandbox_1/Trp20/1'>Trp41</scene> play a key role in the gating mechanism.<ref name="Wu" /> In the closed state, the His37 and Trp41 residues block the channel, preventing proton conductance. <ref name="Lear">PMID:12972146 </ref> | ||
<applet load='1nyj' size='300' frame='true' align='right' caption='The closed state structure of M2 protein H+ channel by solid state NMR spectroscopy. [Stouffer et al, 2008]' /> | |||
== pH Gating == | == pH Gating == | ||
The M2 channel is low-pH gated and has a 50-fold increase in proton conductance when the pH drops from 8.2 down to 4.2.<ref name="Wu" /> The His side chain, a five-membered ring, has two nitrogen atoms.<ref name="Takeuchi" /> At a pH of 7 or higher, only one nitrogen is protonated in the neutral imidazole form.<ref name="Takeuchi" /> However, at a pH of about 5.8, the second nitrogen in one or two helicies becomes protonated and forms the cationic imidazolium form.<ref name="Takeuchi" /> This protonation causes the His residues in each monomer to move away from each other due to electrostatic repulsion.<ref name="Takeuchi" /><ref name="Lear" /><ref name="Wu" /> The bi-protonated His37 residues are then stabilized by the Trp41 residues by a cation-π interaction.<ref name="Wu" /> This allows the channel to open and allow water from the pore to penetrate.<ref name="Lear" /><ref name="Wu" /> This forms what is called a proton-conductive water wire through the gate.<ref name="Wu" /> | The M2 channel is low-pH gated and has a 50-fold increase in proton conductance when the pH drops from 8.2 down to 4.2.<ref name="Wu" /> The His side chain, a five-membered ring, has two nitrogen atoms.<ref name="Takeuchi" /> At a pH of 7 or higher, only one nitrogen is protonated in the neutral imidazole form.<ref name="Takeuchi" /> However, at a pH of about 5.8, the second nitrogen in one or two helicies becomes protonated and forms the cationic imidazolium form.<ref name="Takeuchi" /> This protonation causes the His residues in each monomer to move away from each other due to electrostatic repulsion.<ref name="Takeuchi" /><ref name="Lear" /><ref name="Wu" /> The bi-protonated His37 residues are then stabilized by the Trp41 residues by a cation-π interaction.<ref name="Wu" /> This allows the channel to open and allow water from the pore to penetrate.<ref name="Lear" /><ref name="Wu" /> This forms what is called a proton-conductive water wire through the gate.<ref name="Wu" /> | ||