Co-operative gating interactions in the yeast TOK1 K+ channel

K+通道在所有活细胞中起主要作用，为K+离子跨膜移动提供了一个孔或途径。这些通道是如何构建的，以及它们调节(门)K+通过其毛孔流动的机制是一个密集的研究领域。我们现在知道，所有K+通道的孔都由四个蛋白质结构域组成，每个结构域都有一个孔环和两个侧翼跨膜螺旋。这些通道的门控通常被认为是由每个结构域中独立的蛋白质构象变化引起的，这些变化有助于打开毛孔。酵母K+通道TOK1既受电压控制，又受胞外K+控制。令人惊讶的是，我们最近发现了与每个孔环相关的假定K+结合位点之间存在长距离相互作用的证据。研究结果确定了相邻孔域之间出乎意料的协作性，因此，应该为这些通道的门控提供新的见解。当前项目的扩展将使我们能够系统地探索这些相互作用及其对TOK1 K+通道分子功能的影响。

K+ channels play major roles in all living cells, providing a pore, or pathway for K+ ion movements across membranes. How these channels are constructed and the mechanisms by which they regulate (gate) the flow of K+ through their pores is a field of intense research. We know now that the pores of all K+ channels comprise four protein domains, each with a pore loop and two, flanking transmembrane helices. Gating of these channels has generally been thought to arise from independent protein conformational changes within each domain that contribute to opening the pore. The yeast K+ channel TOK1 is gated both by voltage and by extracellular K+. Surprisingly, we recently uncovered evidence of long-distance interactions between putative K+-binding sites associated with each pore loop. The results identify an unanticipated co-operativity between adjacent pore domains and, thus, should provide new insights into the gating of these channels. An extension to the current project will enable us to systematically explore these interactions and their implications for the molecular functioning of the TOK1 K+ channel.