Kv6
The sparsely populated Kv channel subfamilies Kv5 and Kv6 each contain one member, Kv5.1 and Kv6.1 (see Chandy, K.G. and Gutman, G.A. (1995) In: (R.A. North, ed.), Handbook of Receptors and Channels. Ligand- and Voltage- Gated Ion Channels. CRC Press, Ann Arbor, MI, pp. 1-71) referred to as IK8 and K13, [399]. No function has yet been demonstrated for either of these proteins alone [399].
Kv channels are composed of four subunits that surround the central ion permeation pathway [664]:. Each subunit has six transmembrane domains (S1–S6) and a pore region containing the signature sequence GYG character- istic for potassium channels [667], [619]. Post-translational assembly of tetrameric Kv channels takes place in the ER2 membrane; sub- sequently the channels traffic to the plasma membrane [619], [668]. A highly conserved sequence in the cytoplasmic N terminus of Kv channels, the tetramerization domain or T1 domain, has been shown to play an important role in channel assembly [619], [669]. The T1 domain contains some of the molecular determinants for subfamily-specific homo- or heterotetrameric assembly of Kv alpha-subunits [669], [660],[598], [670]. The most striking difference between the T1 domains of Kv1 (Shaker) and Kv2–4 (non-Shaker) channels is the presence of intersubunit-coordinated Zn2+ ions at the assembly interface in non-Shaker channels. The Zn2+ ions are coordinated by a C3H1 motif embedded in a conserved sequence motif (HX5CX20CC) of the T1 domain, which is located near the distal end of the N terminus [671], [672], [673]. These four amino acids are exposed on the subunit interface, with one histidine and two cysteine residues belonging to one subunit and one cysteine residue belonging to the neighboring subunit [671]. The T1 domain facilitates tetrameric assembly of Kv channels. Kv subunits in which the T1 has been deleted have been reported to assemble in a promiscuous way via their transmembrane domains and to form stable, functional channels, but both the rates and the efficiency of channel assembly are significantly lower in the mutant channels as compared with their wild-type counterparts [668], [674]. Heteromeric assembly of channel subunits is a potential source of diversity of K+ channel properties.
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