Referenced in: K , Kv6 , Kv6.3

Automatically associated channels: Kv4.1

Title: The role of Zn2+ in Shal voltage-gated potassium channel formation.

Authors: Candace Strang, Kumud Kunjilwar, David DeRubeis, David Peterson, Paul J Pfaffinger

Journal, date & volume: J. Biol. Chem., 2003 Aug 15 , 278, 31361-71

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/12754210

Abstract
Voltage-gated potassium channels are formed by the tetramerization of their alpha subunits, in a process that is controlled by their conserved N-terminal T1 domains. The crystal structures of Shaker and Shaw T1 domains reveal interesting differences in structures that are contained within a highly conserved BTB/POZ domain fold. The most surprising difference is that the Shaw T1 domain contains an intersubunit Zn2+ ion that is lacking in the Shaker T1 domain. The Zn2+ coordination motif is conserved in other non-Shaker channels making this the most distinctive difference between these channels and Shaker. In this study we show that Zn2+ is an important co-factor for the tetramerization of isolated Shaw and Shal T1 domains. Addition of Zn2+ increases the amount of tetramer formed, whereas chelation of Zn2+ with phenanthroline blocks tetramerization and causes assembled tetramers to disassemble. Within an intact cell, full-length Shal subunits containing Zn2+ site mutations also fail to form functional channels, with the majority of the protein found to remain monomeric by size exclusion chromatography. Therefore, zinc-mediated tetramerization also is a physiologically important event for full-length functional channel formation.