Arranging the elements of the potassium channel: the T1 domain occludes the cytoplasmic face of the channel.
The voltage-gated potassium channel is currently one of the few membrane proteins where functional roles have been mapped onto specific segments of sequence. Although high-resolution structures of the transmembrane portions of three bacterial potassium channels, the tetramerization domain and the cytoplasmic "ball" are available, their relative spatial arrangement in mammalian channels remains a matter of ongoing debate. Cryo-electron microscopic images of the six transmembrane voltage-gated Kv channel have been reconstructed at up to 18 A resolution, revealing that the T1 domain tetramerizes and is suspended below the transmembrane segments. However, the resolution of these images is insufficient to reveal the location of the third piece of the puzzle, the inactivating ball domain. We have used the aberrant interactions observed in a series of chimaeric channels to establish that an assembled T1 domain restricts access to the cytoplasmic face of the channel, suggesting that the N-terminal "ball and chain" may be confined in the space between the T1 domain and the transmembrane portion of the channel.
Varshney
Anurag
A
National Centre for Biological Sciences, TIFR, UAS-GKVK Campus, 560 065 Bangalore, India.
Chanda
Baron
B
Mathew
M K
MK
D000595:Amino Acid Sequence; D000818:Animals; D002463:Cell Membrane Permeability / Q000502:physiology*; D002478:Cells, Cultured; D003593:Cytoplasm; D015640:Ion Channel Gating / Q000502:physiology*; D008954:Models, Biological; D008956:Models, Chemical; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009865:Oocytes / Q000737:chemistry / Q000502:physiology; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels / Q000737:chemistry* / Q000502:physiology*; D015202:Protein Engineering / Q000379:methods; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship; D014982:Xenopus laevis
D015221:Potassium Channels; D011994:Recombinant Proteins; D011188:Potassium