Comparison of K and mechanosensitive ion channels

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Comparison of K and mechano-sensitive ion
channels
Cha et al. Nature 402813-817
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Why compare KcsA and MscS

• Voltage gated ion channels are extensively
  studied by physiological means
• But the crystal structure is not known
• X-ray structure of bacterial K channel (KcsA)
  exists
• Structure of MscS recently reported. This channel
  responds to voltage changes
• Comparison of these two structures may reveal
  more about voltage gated K channels

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KcsA
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Consensus Sequence of K Channels
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MscS
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Pore region of KcsA
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Charged residues in KcsA

• Thr, Tyr and Asp polar residues in the
  selectivity filter.
• Glu51 and Asp80 are found near the selectivity
  filter.
• The four Glu119 residues form a ring of oxygen at
  the cytoplasmic end.

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Polar residues of MscS
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Polar residues on TM3 of MscS

• Polar residues on TM3 are located at water
  membrane interface.

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Charged residues on MscS

• Charges on the loop reside at the water membrane
  interface.
• Arg74 and Arg46 important for voltage sensing.
• Arg88 the only charged residue that points into
  the pore region.

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Gating mechanism in KcsA

• Fig Residues Ala-92, Val-95 and Met-96 on TM2 are
  in contact with the small pore helix at Thr72
  (purple).
• Thr-72 serves as a fulcrum for the rocking motion
  of TM2.
• Such rocking motion in minimal and does not
  perturb the selectivity filter.

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Conclusion

• KcsA is predominantly non-polar except for the
  selectivity filter. The pore region of MscS is
  non-polar but the rest is very polar.
• Basic residues on MscS may be responsible for
  voltage sensing.
• The gating mechanism of MscS is not studied
  extensively.

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Structural summary of KscA (1BL8)