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Biophys. J. BioFAST: First Published October 14, 2005. doi:10.1529/biophysj.105.066092
© 2005 by the Biophysical Society.

A more recent version of this article appeared on January 1, 2006.
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CHANNELS, RECEPTORS, AND ELECTRICAL SIGNALING

A Ca2+ Binding Domain in RyR1 That Interacts with the Calmodulin Binding Site and Modulates Channel Activity

Liangwen Xiong 1, Jia-Zheng Zhang 1, Rong He 1 and Susan L. Hamilton 1*

1 Baylor College of Medicine

* To whom correspondence should be addressed. E-mail: susanh{at}bcm.tmc.edu.

Submitted on May 11, 2005
Revised on June 6, 2005
Accepted on 27 September 2005


  Abstract
A fragment of RyR1 (amino acids 4064-4210) is predicted to fold similar to at least one lobe of calmodulin and to bind Ca2+. This fragment of RyR1 (R4064-4210) was subcloned, expressed, refolded, and purified. Consistent with the predicted folding pattern, R4064-4210 was found to bind two molecules of Ca2+ and undergo a structural change upon binding Ca2+ that exposes hydrophobic amino acids. R4064-4210 also binds to RyR1, the L-type Ca2+ channel (Cav1.1) and several synthetic calmodulin binding peptides. Both R4064-4210 and a peptide representing the calmodulin binding region of RyR1 (R3614-43) alter the Ca2+ dependence of [3H]ryanodine binding to RyR1, suggesting that they may both be interfering with an intra-molecular interaction between amino acids 4064-4210 and amino acids 3614-43 in the native RyR1 to alter or regulate the response of the channel to changes in Ca2+ concentration. The finding that a domain within RyR1 binds Ca2+ and interacts with calmodulin binding motifs may provide insights into the mechanism for calcium- and calmodulin-dependent regulation of this channel and perhaps for its regulation by the L-type Ca2+ channel.

Key Words: activation, calcium, calmodulin, intra-molecular interactions, ryanodine receptor




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Copyright © 2005 by the Biophysical Society.