Sandbox WWC3: Difference between revisions

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As noted above, the sodium channel consists of an alpha and two beta subunits. However, the alpha subunit is the only part necessary for the function of the channel <ref name = "sod"/>. The alpha subunit, depicted right, consists of four repeating structures, named I through IV <ref name ="struct"> DOI: 10.1111/j.1469-7793.1998.647bp.x </ref> and shown in different colors <scene name='69/696300/Right_one/1'>here</scene>. These structures consist of six transmembrane alpha helices named S1 through S6 <ref name = "struct"/>. Interestingly, each repeating subunit resembles a bacterial K+ channel <ref name = "struct"/>. These subunits fold together to form a central pore, and this complete structure resembles a bacterial Ca2+ channel <ref name = "struct"/>.

=== Gating ===

The S1 through S4 segments make up the gating mechanism <ref name= "crystal"/>. In particular,the S4 segments consist of repeated motifs of a positively charged residue (usually Arg) followed by two hydrophobic residues <ref name= "crystal"/>. This alpha helix is exposed to the membrane electric field, and in response to a depolarization, it is displaced outwards <ref name= "crystal"/>. This causes the channel to open. S4 segments can be seen in red <scene name='69/696300/S4/1'>here</scene>. Surprisingly, each S4 chain does not contribute equally to the gating of this channel. A mutation in one chain may have a much larger effect than a mutation in another S4 chain <ref name= "crystal"/>.. However, these S4 segments are merely sensors. The actual gating mechanism is still up for debate, with the leading contender being the S6 segment. This mechanism would be similar to the gating of the K+ channel <ref name = "struct"/>. The outward movement of the S4 segment moves the S4-S5 linker, which pulls the S5-S6 segments and opens the pore <ref name= "crystal"/>. Overall, the voltage sensing domain makes a rolling motion of the S4-S5 linker around the pore <ref name= "crystal"/>. The S4-S5 linker can be seen <scene name='69/696300/S4_s5_linker/1'>here</scene>.

The S1 through S4 segments make up the gating mechanism <ref name= "crystal"/>. In particular,the S4 segments consist of repeated motifs of a positively charged residue (usually Arg) followed by two hydrophobic residues <ref name= "crystal"/>. This alpha helix is exposed to the membrane electric field, and in response to a depolarization, it is displaced outwards <ref name= "crystal"/>. This causes the channel to open. S4 segments can be seen in red <scene name='69/696300/S4/1'>here</scene>. Surprisingly, each S4 chain does not contribute equally to the gating of this channel. A mutation in one chain may have a much larger effect than a mutation in another S4 chain <ref name= "crystal"/>.. However, these S4 segments are merely sensors. The actual gating mechanism is still up for debate, with the leading contender being the S6 segment. This mechanism would be similar to the gating of the K+ channel <ref name = "struct"/>. The outward movement of the S4 segment moves the S4-S5 linker, which pulls the S5-S6 segments and opens the pore <ref name= "crystal"/>. Overall, the voltage sensing domain makes a rolling motion of the S4-S5 linker around the pore <ref name= "crystal"/>. The S4-S5 linker can be seen <scene name='69/696300/S4_s5_linker/2'>here</scene>.

===Selectivity Filter===

This channel conducts sodium at nearly the rate of free diffusion <ref name= "crystal"/>. This pore consists of an outer funnel-like vestibule, a selectivity filter, a central cavity, and an intracellular activation gate <ref name= "crystal"/>. Unlike the K+ channel, the Na+ channel conducts sodium ions that are hydrated with four water molecules <ref name= "crystal"/>. Much like with the gating mechanism, each domain does not contribute equally to the selectivity of the pore <ref name= "struct"/>, but the channel selects for sodium 100x greater than it selects for any other ion <ref name= "struct"/>.

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@@ Line 8: / Line 8: @@
 As noted above, the sodium channel consists of an alpha and two beta subunits. However, the alpha subunit is the only part necessary for the function of the channel <ref name = "sod"/>. The alpha subunit, depicted right, consists of four repeating structures, named I through IV <ref name ="struct"> DOI: 10.1111/j.1469-7793.1998.647bp.x </ref> and shown in different colors <scene name='69/696300/Right_one/1'>here</scene>. These structures consist of six transmembrane alpha helices named S1 through S6 <ref name = "struct"/>. Interestingly, each repeating subunit resembles a bacterial K+ channel <ref name = "struct"/>. These subunits fold together to form a central pore, and this complete structure resembles a bacterial Ca2+ channel <ref name = "struct"/>.
 === Gating ===
-The S1 through S4 segments make up the gating mechanism <ref name= "crystal"/>. In particular,the S4 segments consist of repeated motifs of a positively charged residue (usually Arg) followed by two hydrophobic residues <ref name= "crystal"/>. This alpha helix is exposed to the membrane electric field, and in response to a depolarization, it is displaced outwards <ref name= "crystal"/>. This causes the channel to open. S4 segments can be seen in red <scene name='69/696300/S4/1'>here</scene>. Surprisingly, each S4 chain does not contribute equally to the gating of this channel. A mutation in one chain may have a much larger effect than a mutation in another S4 chain <ref name= "crystal"/>.. However, these S4 segments are merely sensors. The actual gating mechanism is still up for debate, with the leading contender being the S6 segment. This mechanism would be similar to the gating of the K+ channel <ref name = "struct"/>. The outward movement of the S4 segment moves the S4-S5 linker, which pulls the S5-S6 segments and opens the pore <ref name= "crystal"/>. Overall, the voltage sensing domain makes a rolling motion of the S4-S5 linker around the pore <ref name= "crystal"/>. The S4-S5 linker can be seen <scene name='69/696300/S4_s5_linker/1'>here</scene>.
+The S1 through S4 segments make up the gating mechanism <ref name= "crystal"/>. In particular,the S4 segments consist of repeated motifs of a positively charged residue (usually Arg) followed by two hydrophobic residues <ref name= "crystal"/>. This alpha helix is exposed to the membrane electric field, and in response to a depolarization, it is displaced outwards <ref name= "crystal"/>. This causes the channel to open. S4 segments can be seen in red <scene name='69/696300/S4/1'>here</scene>. Surprisingly, each S4 chain does not contribute equally to the gating of this channel. A mutation in one chain may have a much larger effect than a mutation in another S4 chain <ref name= "crystal"/>.. However, these S4 segments are merely sensors. The actual gating mechanism is still up for debate, with the leading contender being the S6 segment. This mechanism would be similar to the gating of the K+ channel <ref name = "struct"/>. The outward movement of the S4 segment moves the S4-S5 linker, which pulls the S5-S6 segments and opens the pore <ref name= "crystal"/>. Overall, the voltage sensing domain makes a rolling motion of the S4-S5 linker around the pore <ref name= "crystal"/>. The S4-S5 linker can be seen <scene name='69/696300/S4_s5_linker/2'>here</scene>.
 ===Selectivity Filter===
 This channel conducts sodium at nearly the rate of free diffusion <ref name= "crystal"/>. This pore consists of an outer funnel-like vestibule, a selectivity filter, a central cavity, and an intracellular activation gate <ref name= "crystal"/>. Unlike the K+ channel, the Na+ channel conducts sodium ions that are hydrated with four water molecules <ref name= "crystal"/>. Much like with the gating mechanism, each domain does not contribute equally to the selectivity of the pore <ref name= "struct"/>, but the channel selects for sodium 100x greater than it selects for any other ion <ref name= "struct"/>.