Department of Physics and Institute of Molecular Biophysics, Florida State University, Tallahassee, FL 32306, USA.
Trends Biochem Sci. 2012 Feb;37(2):43-8. doi: 10.1016/j.tibs.2011.11.002. Epub 2011 Dec 7.
Association between signaling proteins and their cellular targets is generally thought to be highly specific (implicating a high association constant, K(a)) and, at the same time, transient or short-lived (corresponding to a high dissociation rate constant, k(d)). However, a combination of high K(a) and high k(d) would lead to a high association rate constant (k(a) = K(a)k(d)), which poses a problem because there is a limit to which k(a) can be increased, set by the diffusional approach to form the complex. In this Opinion article, I propose that having the signaling protein disordered before binding to the target provides a way out of this quandary. The intrinsic disorder of the signaling protein would decrease K(a) without sacrificing the specificity of the complex, and thus would allow k(d) to be increased to a range appropriate for signaling.
信号蛋白与其细胞靶标的结合通常被认为是高度特异的（暗示着高的结合常数，K(a)），同时也是短暂或短暂的（对应于高的离解速率常数，k(d)）。然而，高 K(a)和高 k(d)的组合将导致高的结合速率常数（k(a) = K(a)k(d)），这是一个问题，因为 k(a)的增加受到限制，这是由形成复合物的扩散方法决定的。在这篇观点文章中，我提出，在与靶标结合之前使信号蛋白无序，为解决这一困境提供了一种方法。信号蛋白的固有无序性会降低 K(a)，而不会牺牲复合物的特异性，从而使 k(d)增加到适合信号传递的范围。
