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8.A.5 The Voltage-gated K+ Channel β-subunit (Kvβ) Family

Many β-subunits of voltage-gated K+ channels (VIC superfamily, TC #1.A.1.2.1-3) have been sequenced and functionally characterized. The one from rat has been crystallized, and a 2.1 Å resolution structure is available (Gulbis, 2000). The mammalian β-subunits are 350-410 residues in length. They exhibit extensive sequence similarity with many ubiquitous oxidoreductases, with bacterial stress response proteins and with plant auxin-induced proteins. These β-subunits are to some extent interchangeable, and a variety of alternative splice variants are found. They regulate various aspects of the voltage-gated mammalian channels as well as the Drosophila Shaker K+ channel. Thus they affect the voltage-dependence of the activation process, the rate of deactivation and both N-type and C-type inactivation. The conserved C-terminal domain of the β-subunit interacts with the conserved N-terminal hydrophilic domain of the Shaker α-subunit, the same region that determines the compatibility of α-subunits. The hyperkinetic gene of Drosophila encodes a β-subunit of 546 amino acyl residues that when defective produces the Shaker-like, ether-sensitive leg shaking.

Regulatory β-subunits of other channel proteins of the VIC superfamily (TC #1.A.1) function in distinct regulatory capacities, and some are non-homologous to members of the Kvβ family. Myocardial blood flow is control by oxygen-sensing vascular Kvbeta proteins (Ohanyan et al. 2021).


References associated with 8.A.5 family:

Accili, E.A., Y.A. Kuryshev, B.A. Wible, and A.M. Brown. (1998). Separable effects of human Kvbeta1.2 N- and C-termini on inactivation and expression of human Kv1.4. J. Physiol. 512(Pt2): 325-336. 9763623
Gulbis, J.M., M. Zhou, S. Mann, and R. MacKinnon. (2000). Structure of the cytoplasmic β subunit-T1 assembly of voltage-dependent K+ channels. Science 289: 123-127. 10884227
Jan, L.Y. and Y.N. Jan. (1997). Cloned potassium channels from eukaryotes and prokaryotes. Annu. Rev. Neurosci. 20: 91-123. 9056709
Mangubat, E.Z., T.-T. Tseng, and E. Jakobsson. (2003). Phylogenetic analyses of potassium channel auxiliary subunits. J. Mol. Microbiol. Biotechnol. (in press). 12867745
Ohanyan, V., S.M. Raph, M.M. Dwenger, X. Hu, T. Pucci, G.D. Mack, J.B. Moore Iv, W.M. Chilian, A. Bhatnagar, and M.A. Nystoriak. (2021). Myocardial Blood Flow Control by Oxygen Sensing Vascular Kvβ Proteins. Circ Res. [Epub: Ahead of Print] 33499656
Peters, C.J., M. Vaid, A.J. Horne, D. Fedida, and E.A. Accili. (2009). The molecular basis for the actions of KVbeta1.2 on the opening and closing of the KV1.2 delayed rectifier channel. Channels (Austin) 3: 314-322. 19713757
Tipparaju, S.M., S.Q. Liu, O.A. Barski, and A. Bhatnagar. (2007). NADPH binding to β-subunit regulates inactivation of voltage-gated K+ channels. Biochem. Biophys. Res. Commun. 359: 269-276. 17540341