title: Zn2+-binding and molecular determinants of tetramerization in voltage-gated K+ channels.
abstract: 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.
authors.affiliation: The Salk Institute, Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla 92037, USA.
authors.forename: K A
authors.initials: KA
authors.lastname: Bixby
authors.forename: M H
authors.initials: MH
authors.lastname: Nanao
authors.forename: N V
authors.initials: NV
authors.lastname: Shen
authors.forename: A
authors.initials: A
authors.lastname: Kreusch
authors.forename: H
authors.initials: H
authors.lastname: Bellamy
authors.forename: P J
authors.initials: PJ
authors.lastname: Pfaffinger
authors.forename: S
authors.initials: S
authors.lastname: Choe
mesh_terms: 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*
chemical_list: D015221:Potassium Channels; D015032:Zinc