Journal of Biological Chemistry
Volume 270, Issue 42, 20 October 1995, Pages 24761-24768
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Membranes and Bioenergetics
Assembly of Voltage-gated Potassium Channels: CONSERVED HYDROPHILIC MOTIFS DETERMINE SUBFAMILY-SPECIFIC INTERACTIONS BETWEEN THE α-SUBUNITS (∗)

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Voltage-gated potassium (K+) channels are assembled by four identical or homologous α-subunits to form a tetrameric complex with a central conduction pore for potassium ions. Most of the cloned genes for the α-subunits are classified into four subfamilies: Kv1 (Shaker), Kv2 (Shab), Kv3 (Shaw), and Kv4 (Shal). Subfamily-specific assembly of heteromeric K+ channel complexes has been observed in vitro and in vivo, which contributes to the diversity of K+ currents. However, the molecular codes that mediate the subfamily-specific association remain unknown. To understand the molecular basis of the subfamily-specific assembly, we tested the protein-protein interactions of different regions of α-subunits. We report here that the cytoplasmic NH2-terminal domains of Kv1, Kv2, Kv3, and Kv4 subfamilies each associate to form homomultimers. Using the yeast two-hybrid system and eight K+ channel genes, two genes (one isolated from rat and one from Drosophila) from each subfamily, we demonstrated that the associations to form heteromultimers by the NH2-terminal domains are strictly subfamily-specific. These subfamily-specific associations suggest a molecular basis for the selective formation of heteromultimeric channels in vivo.

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This work was supported in part by a grant from the National Institutes of Health (to M. L.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

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Investigators of Howard Hughes Medical Institutes (Y.-N. J. and L. Y. J.).