| Structural highlights
Disease
[KCNN4_HUMAN] The disease is caused by mutations affecting the gene represented in this entry.
Function
[KCNN4_HUMAN] Forms a voltage-independent potassium channel that is activated by intracellular calcium (PubMed:26148990). Activation is followed by membrane hyperpolarization which promotes calcium influx. Required for maximal calcium influx and proliferation during the reactivation of naive T-cells. The channel is blocked by clotrimazole and charybdotoxin but is insensitive to apamin (PubMed:17157250, PubMed:18796614).[1] [2] [3]
Publication Abstract from PubMed
KCa3.1 (also known as SK4 or IK1) is a mammalian intermediate-conductance potassium channel that plays a critical role in the activation of T cells, B cells, and mast cells, effluxing potassium ions to maintain a negative membrane potential for influxing calcium ions. KCa3.1 shares primary sequence similarity with three other (low-conductance) potassium channels: KCa2.1, KCa2.2, and KCa2.3 (also known as SK1-3). These four homotetrameric channels bind calmodulin (CaM) in the cytoplasmic region, and calcium binding to CaM triggers channel activation. Unique to KCa3.1, activation also requires phosphorylation of a single histidine residue, His358, in the cytoplasmic region, which relieves copper-mediated inhibition of the channel. Near the cytoplasmic C-terminus of KCa3.1 (and KCa2.1-2.3), secondary-structure analysis predicts the presence of a coiled-coil/heptad repeat. Here, we report the crystal structure of the C-terminal coiled-coil region of KCa3.1, which forms a parallel four-helix bundle, consistent with the tetrameric nature of the channel. Interestingly, the four copies of a histidine residue, His389, in an 'a' position within the heptad repeat, are observed to bind a copper ion along the four-fold axis of the bundle. These results suggest that His358, the inhibitory histidine in KCa3.1, might coordinate a copper ion through a similar binding mode.
Crystal structure of the C-terminal four-helix bundle of the potassium channel KCa3.1.,Ji T, Corbalan-Garcia S, Hubbard SR PLoS One. 2018 Jun 28;13(6):e0199942. doi: 10.1371/journal.pone.0199942., eCollection 2018. PMID:29953543[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Srivastava S, Li Z, Ko K, Choudhury P, Albaqumi M, Johnson AK, Yan Y, Backer JM, Unutmaz D, Coetzee WA, Skolnik EY. Histidine phosphorylation of the potassium channel KCa3.1 by nucleoside diphosphate kinase B is required for activation of KCa3.1 and CD4 T cells. Mol Cell. 2006 Dec 8;24(5):665-675. doi: 10.1016/j.molcel.2006.11.012. PMID:17157250 doi:http://dx.doi.org/10.1016/j.molcel.2006.11.012
- ↑ Srivastava S, Zhdanova O, Di L, Li Z, Albaqumi M, Wulff H, Skolnik EY. Protein histidine phosphatase 1 negatively regulates CD4 T cells by inhibiting the K+ channel KCa3.1. Proc Natl Acad Sci U S A. 2008 Sep 23;105(38):14442-6. doi:, 10.1073/pnas.0803678105. Epub 2008 Sep 16. PMID:18796614 doi:http://dx.doi.org/10.1073/pnas.0803678105
- ↑ Rapetti-Mauss R, Lacoste C, Picard V, Guitton C, Lombard E, Loosveld M, Nivaggioni V, Dasilva N, Salgado D, Desvignes JP, Beroud C, Viout P, Bernard M, Soriani O, Vinti H, Lacroze V, Feneant-Thibault M, Thuret I, Guizouarn H, Badens C. A mutation in the Gardos channel is associated with hereditary xerocytosis. Blood. 2015 Sep 10;126(11):1273-80. doi: 10.1182/blood-2015-04-642496. Epub 2015 , Jul 6. PMID:26148990 doi:http://dx.doi.org/10.1182/blood-2015-04-642496
- ↑ Ji T, Corbalan-Garcia S, Hubbard SR. Crystal structure of the C-terminal four-helix bundle of the potassium channel KCa3.1. PLoS One. 2018 Jun 28;13(6):e0199942. doi: 10.1371/journal.pone.0199942., eCollection 2018. PMID:29953543 doi:http://dx.doi.org/10.1371/journal.pone.0199942
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