6D42

Crystal structure of the KCa3.1 C-terminal four-helix bundle (with copper)

Summary for 6D42

• Entry DOI: 10.2210/pdb6d42/pdb
• Descriptor: Intermediate conductance calcium-activated potassium channel protein 4, COPPER (II) ION (3 entities in total)
• Functional Keywords: four-helix bundle, copper, membrane protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 9261.13

Authors

Hubbard, S.R.,Ji, T. (deposition date: 2018-04-17, release date: 2018-07-11, Last modification date: 2019-12-18)

Primary citation

Ji, T.,Corbalan-Garcia, S.,Hubbard, S.R.
Crystal structure of the C-terminal four-helix bundle of the potassium channel KCa3.1.
PLoS ONE, 13:e0199942-e0199942, 2018

PubMed Abstract: 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.

PubMed: 29953543
DOI: 10.1371/journal.pone.0199942

Experimental method

X-RAY DIFFRACTION (1.75013644453 Å)