Zn2+-binding and molecular determinants of tetramerization in voltage-gated K+ channels.
The N-terminal, cytoplasmic tetramerization domain (T1) of voltage-gated K+ channels encodes molecular determinants for subfamily-specific assembly of alpha-subunits into functional tetrameric channels. Crystal structures of T1 tetramers from Shaw and Shaker subfamilies reveal a common four-layered scaffolding. Within layer 4, on the hypothetical membrane-facing side of the tetramer, the Shaw T1 tetramer contains four zinc ions; each is coordinated by a histidine and two cysteines from one monomer and by one cysteine from an adjacent monomer. The amino acids involved in coordinating the Zn2+ ion occur in a HX5CX20CC sequence motif that is highly conserved among all Shab, Shaw and Shal subfamily members, but is not found in Shaker subfamily members. We demonstrate by coimmunoprecipitation that a few characteristic residues in the subunit interface are crucial for subfamily-specific tetramerization of the T1 domains.
Bixby
K A
KA
The Salk Institute, Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla 92037, USA.
Nanao
M H
MH
Shen
N V
NV
Kreusch
A
A
Bellamy
H
H
Pfaffinger
P J
PJ
Choe
S
S
D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D008969:Molecular Sequence Data; D015221:Potassium Channels / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011487:Protein Conformation; D016415:Sequence Alignment; D017421:Sequence Analysis; D015032:Zinc / Q000378:metabolism*
D015221:Potassium Channels; D015032:Zinc