comparison of k+ and mechano-sensitive ion channels

Comparison of K+ and mechano-sensitive ion channels

Cha et al. Nature 402:813-817

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

KcsA

Consensus Sequence of K+ Channels

MscS

Pore region of KcsA

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.

Polar residues of MscS

Polar residues on TM3 of MscS

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

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.

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.

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.

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