Rostovtseva T K, Liu T T, Colombini M, Parsegian V A, Bezrukov S M
Laboratory of Physical and Structural Biology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-0924, USA.
Proc Natl Acad Sci U S A. 2000 Jul 5;97(14):7819-22. doi: 10.1073/pnas.140115397.
The monomeric VDAC channel shows an accelerated pH titration of its transport properties with a Hill coefficient of about 2. This manifests itself as a sharp peak in conductance noise as well as a fast change in channel selectivity with pH. On the basis of the known structure of this channel, we propose that this cooperativity arises from a mechanically linked mobile pair of ionizable groups. Concerted movement of these groups between two states changes the distance from nearby electrostatic charge to influence the pK of the groups. This model of pH-dependent motion produces positive cooperative behavior that fits the observations without need for subunits or identifiable domains within the protein. The mathematical formalism has never required such domains, but these are generally considered an essential part of cooperative behavior in proteins. The present proposal reduces the size of a cooperative unit to a minimum, extending the limits of what is perceived to be possible. Together with large-scale conformational transitions, these subtle cooperative structural changes may allow proteins to adapt, with high sensitivity, to changes in their environment. They might also be relatively easy to engineer into a protein.
单体电压依赖性阴离子通道（VDAC）的运输特性在pH滴定过程中加速，希尔系数约为2。这表现为电导噪声中的尖锐峰值以及通道选择性随pH的快速变化。基于该通道的已知结构，我们提出这种协同性源于一对机械连接的可电离基团的移动对。这些基团在两种状态之间的协同运动改变了与附近静电荷的距离，从而影响基团的pK值。这种pH依赖性运动模型产生了正协同行为，符合观察结果，无需蛋白质中的亚基或可识别结构域。数学形式主义从未需要这样的结构域，但这些通常被认为是蛋白质协同行为的重要组成部分。目前的提议将协同单元的大小降至最低，扩展了人们认为可能的极限。与大规模构象转变一起，这些微妙的协同结构变化可能使蛋白质能够高度敏感地适应其环境变化。它们也可能相对容易被设计到蛋白质中。
