REVEALING THE ARCHITECTURE OF A K+ CHANNEL PORE THROUGH MUTANT CYCLES WITH A PEPTIDE INHIBITOR
REVEALING THE ARCHITECTURE OF A K+ CHANNEL PORE THROUGH MUTANT CYCLES WITH A PEPTIDE INHIBITOR
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DOI：
10.1126/science.7716527
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发表时间：
1995-04-14
期刊：
影响因子：
56.9
通讯作者：
MACKINNON, R
中科院分区：
文献类型：
--
作者：
HIDALGO, P;MACKINNON, R
热力学突变体循环提供了一种形式主义，研究在蛋白质-蛋白质复合物的相互作用表面上的氨基酸之间的能量耦合。这种方法被应用到振动钾通道和高亲和力肽抑制剂（蝎毒素），结合到其孔入口。成对相互作用的分配定义了通道氨基酸相对于已知抑制剂结构的空间排列。通过要求其氨基末端边界距离中心轴12至15埃，对Shaker通道成孔区域施加了强约束。该方法直接适用于钠、钙和其他离子通道，其中抑制剂或调节蛋白以高亲和力结合。
Thermodynamic mutant cycles provide a formalism for studying energetic coupling between amino acids on the interaction surface in a protein-protein complex. This approach was applied to the Shaker potassium channel and to a high-affinity peptide inhibitor (scorpion toxin) that binds to its pore entryway. The assignment of pairwise interactions defined the spatial arrangement of channel amino acids with respect to the known inhibitor structure. A strong constraint was placed on the Shaker channel pore-forming region by requiring its amino-terminal border to be 12 to 15 angstroms from the central axis. This method is directly applicable to sodium, calcium, and other ion channels where inhibitor or modulatory proteins bind with high affinity.