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Review
. 2022 Sep 1;37(5):0.
doi: 10.1152/physiol.00005.2022.

Kv Channel Ancillary Subunits: Where Do We Go from Here?

Geoffrey W Abbott  1
Affiliations
Review

Kv Channel Ancillary Subunits: Where Do We Go from Here?

Geoffrey W Abbott. Physiology (Bethesda). .

Abstract

Voltage-gated potassium (Kv) channels each comprise four pore-forming α-subunits that orchestrate essential duties such as voltage sensing and K+ selectivity and conductance. In vivo, however, Kv channels also incorporate regulatory subunits-some Kv channel specific, others more general modifiers of protein folding, trafficking, and function. Understanding all the above is essential for a complete picture of the role of Kv channels in physiology and disease.

Keywords: KCNE; KCNQ; MinK-related peptide; cardiac arrhythmia; potassium channel.

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Conflict of interest statement

The author’s research is partially funded by an NIGMS R35 MIRA (GM130377), an award mechanism discussed in this article.

Figures

FIGURE 1.
FIGURE 1.
Topology and stoichiometry of Kv channel α and ancillary subunits A: membrane span topology of Kv α and KCNE subunits. B: representation of a KCNQ1-KCNE2 complex depicting 4 KCNQ1 and 4 KCNE2 subunits. C: representation of a Kvα-Kvβ complex depicting 4 Kvα and 4 Kvβ subunits. D: representation of a Kv4-KChIP-DPPX complex depicting 4 of each subunit type. VSD, voltage sensing domain.
FIGURE 2.
FIGURE 2.
High-resolution structures of bipartite Kv channel complexes: KCNA channel regulation by Kvβ subunits A: X-ray crystallographic structure of Kv1.1 (KCNA1) cytosolic T1 domains (brown) in complex with Kvβ2 subunits (green). Image from the RCSB PDB (rcsb.org) of PDB ID 1EXB (Ref. ; PDB: https://www.rcsb.org/structure/1EXB). B: X-ray crystallographic structure of Kv1.2 (KCNA2) channel in complex with Kvβ2 subunits (green). Image from the RCSB PDB (rcsb.org) of PDB ID 2A79 (Ref. ; PDB: https://www.rcsb.org/structure/2A79).
FIGURE 3.
FIGURE 3.
High-resolution structures of tripartite potassium channel complexes A: cryo-electron microscopy (cryo-EM) structure of Kv4.2 in complex with DPP6S and KChIP1 (red/blue, orange and gold, respectively, in top left grouping). Image from the RCSB PDB (rcsb.org) of PDB ID 7E8H (Ref. ; https://www.rcsb.org/structure/7E8H). B: cryo-EM structure of KCNQ1 in complex with KCNE3 and calmodulin (dark green, purple, and light green, respectively, in top left grouping of left panel; cobalt, gray, and pink, respectively, in top left grouping of right panel) in the absence (left) and presence (right) of phosphatidylinositol 4,5-bisphosphate (PIP2). Images from the RCSB PDB (rcsb.org) of PDB ID 6V00 (left) and 6V01 (right) [Ref. ; PDB: https://www.rcsb.org/structure/6V00 (left), https://www.rcsb.org/structure/6V01 (right)].
FIGURE 4.
FIGURE 4.
High-resolution structure of a multipartite cation channel-transporter complex Cryo-electron microscopy (cryo-EM) structure of a CatSpermasome, a multipartite cation channel-transporter complex consisting of a pore tetramer comprising CatSper1-4 and various ancillary subunits including a single subunit per complex of the organic anion transporter SLCO6C1 (red). Image from the RCSB PDB (rcsb.org) of PDB ID 7EEB (Ref. ; PDB: https://www.rcsb.org/structure/7EEB).
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