Potassium channel Xavier

The structure is comprised of 4 identical subunits. Each subunit has a and one fourth of the pore. There is the marked between the parallel lines in the figure. This region houses the , composed of interwoven helices in a teepee conformation, the all-important , providing the channel with its remarkable 10,00 fold selectivity for K⁺ ions over Na⁺ ions and the which is uses well placed arginine and acidic residues to determine the membrane polarity and open/close the channel in response.^[2]

See what the The looks like vs. The (1k4c). Or view the morph of the ().

Overall mechanism

The main steps that potassium ions go trough when leaving the cell are:

• Entering the hydrophobic pocket
• Aqueous cavity and desolvation
• Selectivity filter
• Explaining the voltage sensor and closing/opening of channel

Entering the hydrophobic pocket

It is important to notice that with the exception of the selectivity filter, the pore lining is . The entrance of the channel, at the bottom of the 34Å pore containing transmembrane region lies a number of which help form a seal between the pore and the intracellular cytoplasm.

Aqueous cavity and desolvation

This hydrophobic lining provides an inert surface over which the diffusing ion can slide unimpaired. At the end of the hydrophobic porus there is an (). At this point, K⁺ ions find a position of hydration and get ready to be dehydrated and get into the selectivity filter.

Selectivity Filter and Pore

At this point it is clear to see where the channels remarkable selectivity comes from. When entering the , K⁺ ions are first dehydrated, shedding up to 8 waters of the .

Why K+ and not Na+

To stabilize these naked ions, () bind the K⁺ ions. The distance between K⁺ ion and carbonyl oxygen is at to accommodate K⁺ ions but not Na⁺, ions which are too small. If a Na⁺ ion were to lose its water shell, the carbonyl oxygens could not successfully stabilize it in its naked form and thus it is energetically unfavorable for a Na⁺ ion to enter the channel.

Knock on and polarity of helices

There is room within the selectivity filter for . This, as it turns out, is crucial as the presence of the positive cations in close proximity to one another effectively pushes the potassium ions through the filter via electrostatic forces. This helps explain how the potassium channel can have such a rapid turnover rate. Also, the , with the , helps pull the positively charged ions through the channel quickly. Compared to the (1k4c), when exposed to a low concentration of potassium, the channel assumes a (1k4d) which is sealed shut via interactions with water molecules.^[1]

      It is instructive to follow the path of a potassium ion as it enters the cell through the . Upon , the K⁺ ion first comes into contact with the . The solved structure of the potassium channel by MacKinnon et al. revealed where the channels remarkable selectivity comes from. When entering the , K⁺ ions are first dehydrated, shedding up to 8 waters. To stabilize these naked ions, () bind the K⁺ ions. The distance between K⁺ ion and carbonyl oxygen is at to accommodate K⁺ ions but not Na⁺, ions which are too small. If a Na⁺ ion were to lose its water shell, the carbonyl oxygens could not successfully stabilize it in its naked form and thus it is energetically unfavorable for a Na⁺ ion to enter the channel. There is room within the selectivity filter for . This, as it turns out, is crucial as the presence of the positive cations in close proximity to one another effectively pushes the potassium ions through the filter via electrostatic forces. This helps explain how the potassium channel can have such a rapid turnover rate.^[3] Also, the , with the , helps pull the positively charged ions through the channel quickly. Compared to the (1k4c), when exposed to a low concentration of potassium, the channel assumes a (1k4d) which is sealed shut via interactions with water molecules.^[1]

      The only makes up the beginning of the . With the exception of the selectivity filter, the pore lining is . This hydrophobic lining provides an inert surface over which the diffusing ion can slide unimpaired. Immediately following the selectivity filter is an (). K⁺ ions, after passing through the filter, rehydrate in this cavity, helping overcome much of the energetic difficulty of having a positively charged cation within a hydrophobic membrane. At the bottom of the 34Å pore containing transmembrane region lies a number of which help form a seal between the pore and the intracellular cytoplasm.^[3]

Voltage Sensor

      Channel pore opening is dependent on the membrane voltage, a characteristic that is “sensed” by the . The voltage sensor is comprised of , S0, S1, S2, S3, S4, & S5. Negatively charged sensor residues are either located in the , consisting of Glu 183 (in the 2r9r structure) and Glu 226, or in the consisting of Glu 154, Glu 236, and Asp 259. The external cluster is exposed to solvent while the internal cluster is buried. acts as a separator between the two clusters.^[2] The 7 of the voltage sensor are located on the S4 helix. Lys 302 and Arg 305 with the internal negative cluster while Arginines 287, 290, 293, 296 and 299 are (). When the voltage sensor is exposed to a strong negative electric field in the intracellular membrane, the positive gating charges shift inward with the α-carbon of Arg 290 coming in close proximity to Phe 233. This shift effectively squeezes the pore shut, closing the intracellular-extracellular pathway. For a comparison see: The Channel vs. The (1k4c) Channel.^[2] Or view the morph of the ().

      Overall, Potassium channels are remarkable structures that allow for near diffusion limit transfer of molecules with sub-angstrom specificity. Our understanding of the structure of Potassium Channels has opened up the potential for therapeutic intervention into Potassium channel related diseases.