TY - JOUR
T1 - Distinct functional stoichiometry of potassium channel β subunits
AU - Xu, Jia
AU - Yu, Weifeng
AU - Wright, Jerry M.
AU - Raab, Ronald W.
AU - Li, Min
PY - 1998/2/17
Y1 - 1998/2/17
N2 - Shaker-type potassium channels play important roles in determining the electrical excitability of cells. The native channel complex is thought to be formed by four pore-forming α subunits that provide four interaction sites for auxiliary modulatory Kvβ subunits. Because Kvβ subunits possess diverse modulatory activities including either up-regulation or down-regulation of potassium currents, differential assembly of the α-β complex could give rise to diverse current properties. However, the detailed physical and functional stoichiometry of the α-β complex remains unknown. Kvβ1 subunits reduce potassium currents through inactivation, whereas Kvβ2 subunits enhance potassium currents by inhibiting the Kvβ1-mediated inactivation and at the same time by promoting the surface expression of certain potassium channels. In this report we show that Kvβ1 and Kvβ2 of the Shaker-type potassium channels display distinct functional stoichiometry to interact with the Kv1 α subunits, a subfamily of Shaker-type potassium channels. The interaction of Kvβ1 subunits with α subunits is consistent with the α4β(n) model, where n equals 0, 1, 2, 3, or 4, depending upon the relative concentration of α and β subunits. The α4β(n) stoichiometry allows for gradual changes of the Kvβ1-mediated inactivation. In contrast, Kvβ2 subunits self-associate to form oligomers and interact with the α subunits via α4β4 stoichiometry, which permits effective multivalent associations with α subunits. Such distinct functional stoichiometry of Kvβ1 and Kvβ2 provides a molecular mechanism that is well suited to their contrasting activities of up-regulation or down-regulation of potassium currents.
AB - Shaker-type potassium channels play important roles in determining the electrical excitability of cells. The native channel complex is thought to be formed by four pore-forming α subunits that provide four interaction sites for auxiliary modulatory Kvβ subunits. Because Kvβ subunits possess diverse modulatory activities including either up-regulation or down-regulation of potassium currents, differential assembly of the α-β complex could give rise to diverse current properties. However, the detailed physical and functional stoichiometry of the α-β complex remains unknown. Kvβ1 subunits reduce potassium currents through inactivation, whereas Kvβ2 subunits enhance potassium currents by inhibiting the Kvβ1-mediated inactivation and at the same time by promoting the surface expression of certain potassium channels. In this report we show that Kvβ1 and Kvβ2 of the Shaker-type potassium channels display distinct functional stoichiometry to interact with the Kv1 α subunits, a subfamily of Shaker-type potassium channels. The interaction of Kvβ1 subunits with α subunits is consistent with the α4β(n) model, where n equals 0, 1, 2, 3, or 4, depending upon the relative concentration of α and β subunits. The α4β(n) stoichiometry allows for gradual changes of the Kvβ1-mediated inactivation. In contrast, Kvβ2 subunits self-associate to form oligomers and interact with the α subunits via α4β4 stoichiometry, which permits effective multivalent associations with α subunits. Such distinct functional stoichiometry of Kvβ1 and Kvβ2 provides a molecular mechanism that is well suited to their contrasting activities of up-regulation or down-regulation of potassium currents.
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U2 - 10.1073/pnas.95.4.1846
DO - 10.1073/pnas.95.4.1846
M3 - Article
C2 - 9465105
AN - SCOPUS:0032539628
SN - 0027-8424
VL - 95
SP - 1846
EP - 1851
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 4
ER -