| Structural highlights
Disease
[KCNE3_HUMAN] Brugada syndrome;Hypokalemic periodic paralysis.
Function
[KCNE3_HUMAN] Ancillary protein that assembles as a beta subunit with a voltage-gated potassium channel complex of pore-forming alpha subunits. Modulates the gating kinetics and enhances stability of the channel complex. Assembled with KCNB1 modulates the gating characteristics of the delayed rectifier voltage-dependent potassium channel KCNB1 (PubMed:12954870). Associated with KCNC4/Kv3.4 is proposed to form the subthreshold voltage-gated potassium channel in skeletal muscle and to establish the resting membrane potential (RMP) in muscle cells. Associated with KCNQ1/KCLQT1 may form the intestinal cAMP-stimulated potassium channel involved in chloride secretion that produces a current with nearly instantaneous activation with a linear current-voltage relationship.[UniProtKB:Q9JJV7][1] [2]
Publication Abstract from PubMed
The single-span membrane protein KCNE3 modulates a variety of voltage-gated ion channels in diverse biological contexts. In epithelial cells, KCNE3 regulates the function of the KCNQ1 potassium ion (K(+)) channel to enable K(+) recycling coupled to transepithelial chloride ion (Cl(-)) secretion, a physiologically critical cellular transport process in various organs and whose malfunction causes diseases, such as cystic fibrosis (CF), cholera, and pulmonary edema. Structural, computational, biochemical, and electrophysiological studies lead to an atomically explicit integrative structural model of the KCNE3-KCNQ1 complex that explains how KCNE3 induces the constitutive activation of KCNQ1 channel activity, a crucial component in K(+) recycling. Central to this mechanism are direct interactions of KCNE3 residues at both ends of its transmembrane domain with residues on the intra- and extracellular ends of the KCNQ1 voltage-sensing domain S4 helix. These interactions appear to stabilize the activated "up" state configuration of S4, a prerequisite for full opening of the KCNQ1 channel gate. In addition, the integrative structural model was used to guide electrophysiological studies that illuminate the molecular basis for how estrogen exacerbates CF lung disease in female patients, a phenomenon known as the "CF gender gap."
Structural basis for KCNE3 modulation of potassium recycling in epithelia.,Kroncke BM, Van Horn WD, Smith J, Kang C, Welch RC, Song Y, Nannemann DP, Taylor KC, Sisco NJ, George AL Jr, Meiler J, Vanoye CG, Sanders CR Sci Adv. 2016 Sep 9;2(9):e1501228. doi: 10.1126/sciadv.1501228. eCollection 2016 , Sep. PMID:27626070[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Schroeder BC, Waldegger S, Fehr S, Bleich M, Warth R, Greger R, Jentsch TJ. A constitutively open potassium channel formed by KCNQ1 and KCNE3. Nature. 2000 Jan 13;403(6766):196-9. PMID:10646604 doi:http://dx.doi.org/10.1038/35003200
- ↑ McCrossan ZA, Lewis A, Panaghie G, Jordan PN, Christini DJ, Lerner DJ, Abbott GW. MinK-related peptide 2 modulates Kv2.1 and Kv3.1 potassium channels in mammalian brain. J Neurosci. 2003 Sep 3;23(22):8077-91. PMID:12954870
- ↑ Kroncke BM, Van Horn WD, Smith J, Kang C, Welch RC, Song Y, Nannemann DP, Taylor KC, Sisco NJ, George AL Jr, Meiler J, Vanoye CG, Sanders CR. Structural basis for KCNE3 modulation of potassium recycling in epithelia. Sci Adv. 2016 Sep 9;2(9):e1501228. doi: 10.1126/sciadv.1501228. eCollection 2016 , Sep. PMID:27626070 doi:http://dx.doi.org/10.1126/sciadv.1501228
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