comparison of k+ and mechano- sensitive ion channels cha et al. nature 402:813-817
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Comparison of K+ and mechano-sensitive ion channels
Cha et al. Nature 402:813-817
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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)
Name Residues Conserved residues
TM1 29-52 G30, L35, S44, E50 and A51
loop 53-61 G88,
Pore helix 62-73 W68, W69, T72
Selectivity filter & loop
74 to 79 selectivity filter80-84 loop
P83
TM2 85-119 G88, V91, A98, G99, L104 and F116