Title: Zn2+-binding and molecular determinants of tetramerization in voltage-gated K+ channels.

Authors: K A Bixby, M H Nanao, N V Shen, A Kreusch, H Bellamy, P J Pfaffinger, S Choe

Journal, date & volume: Nat. Struct. Biol., 1999 Jan , 6, 38-43

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/9886290

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.