Department of Medicine, University of Illinois at Chicago, USA.
Biophys J. 2011 Jan 19;100(2):381-9. doi: 10.1016/j.bpj.2010.11.086.
Kir channels play an important role in setting the resting membrane potential and modulating membrane excitability. A common feature of several Kir channels is that they are regulated by cholesterol. Yet, the mechanism by which cholesterol affects channel function is unclear. We recently showed that the cholesterol sensitivity of Kir2 channels depends on several CD-loop residues. Here we show that this cytosolic loop is part of a regulatory site that also includes residues in the G-loop, the N-terminus, and the connecting segment between the C-terminus and the inner transmembrane helix. Together, these residues form a cytosolic belt that surrounds the pore of the channel close to its interface with the transmembrane domain, and modulate the cholesterol sensitivity of the channel. Furthermore, we show that residues in this cluster are correlated with residues located in the most flexible region of the G-loop, the major cytosolic gate of Kir2.1, implying that the importance of these residues extends beyond their effect on the channel's cholesterol sensitivity. We suggest that the residues of the cholesterol sensitivity belt are critical for channel gating.
钾离子通道在设定静息膜电位和调节膜兴奋性方面发挥着重要作用。几个钾离子通道的一个共同特征是它们受胆固醇调节。然而，胆固醇影响通道功能的机制尚不清楚。我们最近表明，Kir2 通道的胆固醇敏感性取决于几个 CD 环残基。在这里，我们表明这个胞质环是一个调节位点的一部分，该调节位点还包括 G 环、N 端和 C 端与跨膜螺旋之间的连接段中的残基。这些残基共同形成一个胞质带，环绕通道的孔，靠近其与跨膜域的界面，并调节通道的胆固醇敏感性。此外，我们表明，该簇中的残基与位于 G 环最灵活区域的残基相关，G 环是 Kir2.1 的主要胞质门，这意味着这些残基的重要性超出了它们对通道胆固醇敏感性的影响。我们认为，胆固醇敏感性带的残基对于通道门控至关重要。
