Abstract

Abtract

BK channel

BK channel

A Model for the BK channel

A working structural model for the BK channel was constructed based on amino acid sequence alignments and structural components shared by:

1.       The MthK channel [prokaryote]
2.       The paddle chimera voltage-dependent K+ channel
3.       BK gating ring

Initially the channel structure from the paddle chimera (residues 140-409) was superimposed on the MthK channel structure by aligning the main chain atoms from the pore helix and selectivity filter (S5 and S6 helix [see fig. 13], with a root mean square deviation [measuring differences between values predicted by a model and values actually observed] of 0.87Å.
Click to view an animated 3D model of the: Paddle Chimera channel (above) or the MthK channel (below).
Fig. 13: The Tetrameric structure of the paddle chimera voltage-dependant K+ channel (above) and the tetrameric structure of the prokaryotic MthK potassium channel (below). The sequences that were used to align the two proteins when the researchers aligned them. Red: S5 helix; Blue: Pore helix; Yellow: S6 helix. As we can see, the two structures are relatively similar structurally.

The BK gating ring was subsequently superimposed on the MthK channel by matching secondary structural elements of the BK RCK1 domain and the MthK RCK domain. This used the same method as before and allowed the alignment due to tertiary structure similarities between the two molecules.
Fig. 14: Sequences that were aligned in order to superimpose the different potassium channel homologues. (hSlo BK is the human BK channel). (Adapted from Peng's Yuan, et. al's paper).
This gave rise to a model for a single subunit of the BK channel and hence the tetrameric structure was generated as shown:
Fig. 15: Tetrameric structure of the human BK channel (adapted from Peng's Yuan, et. al's paper).

The authors believe that their model for the BK channel might correspond to the real structure because the CTD tetramer fits well against the surface of the paddle chimera channel and it has ridges that fit into grooves that exist between the the voltage sensing helices and the pore helix [see fig. 1].


Video 2: A 3D animation created to show the completed tetrameric paddle chimera channel in all orientations



Video 3: A 3D animation created to show the completed octameric MthK channel in all orientations

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