J. Biol. Chem., Vol. 278, Issue 33, 31361-31371, August 15, 2003


The Role of Zn2+ in Shal Voltage-gated Potassium Channel Formation* 

Candace Strang, Kumud Kunjilwar, David DeRubeis, David Peterson and Paul J. Pfaffinger**  

From the Neuroscience Division, Baylor College of Medicine, Houston, Texas 77030 

Voltage-gated potassium channels are formed by the tetramerization of their a-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. 



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Received for publication, April 23, 2003 

* This work was supported by Grants R01 NS31583 and P01 NS37444 from the National 
Institutes of Health and the cores of the Baylor College of Medicine Mental Retardation 
Research Center Grant HD24064. The costs of publication of this article were defrayed in 
part by the payment of page charges. This article must therefore be hereby marked 
"advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. 

** To whom correspondence should be addressed: Neuroscience Division, S630, Baylor 
College of Medicine, One Baylor Plaza, Houston, TX 77030. 
E-mail: ppfaff@cns.neusc.bcm.tmc.edu. 



Copyright © 2003 by the American Society for Biochemistry and Molecular Biology.