Schmidt Elizabeth Spanbauer, Forlemu Neville Y, Njabon Eric N, Thomasson Kathryn A
University of North Dakota, Chemistry Department, 151 Cornell St. Stop 9024, Grand Forks, ND 58202-9024.
J Undergrad Chem Res. 2010 Fall;9(4):87-96.
Functional protein-protein interactions are essential for many physiological processes. For example, the association of glycolytic enzymes to F-actin is proposed to be one mechanism through which glycolytic enzymes are compartmentalized, and as a result, play essential roles such as regulation of the glycolytic pathway and increasing glycolytic flux. Many glycolytic enzymes including fructose-1,6-bisphophate aldolase, glyceraldedhye-3-phosphate dehydrogenase, and lactate dehydrogenase bind F-actin strongly. Other glycolytic enzymes including triose phosphate isomerase (TPI) do not interact with F-actin significantly. Herein, Brownian dynamics (BD) simulations determine the energetics of the association of F-actin with the glycolytic enzyme triose phosphate isomerase as a function of ionic strength. This is the first thorough control study examining how well BD reproduces the experimental observations that the binding of TPI to F-actin is very weak and falls off rapidly as ionic strength increases. The BD results confirm experimental observations that the degree of association diminishes as ionic strength increases and that the interaction of TPI with F-actin is weakly nonspecific to nonexistent.
功能性蛋白质-蛋白质相互作用对许多生理过程至关重要。例如，糖酵解酶与F-肌动蛋白的结合被认为是糖酵解酶进行区室化的一种机制，因此，发挥着诸如调节糖酵解途径和增加糖酵解通量等重要作用。许多糖酵解酶，包括果糖-1,6-二磷酸醛缩酶、甘油醛-3-磷酸脱氢酶和乳酸脱氢酶，都能与F-肌动蛋白强烈结合。其他糖酵解酶，包括磷酸丙糖异构酶（TPI），则与F-肌动蛋白没有显著相互作用。在此，布朗动力学（BD）模拟确定了F-肌动蛋白与糖酵解酶磷酸丙糖异构酶结合的能量学与离子强度的函数关系。这是第一项全面的对照研究，考察了BD在多大程度上能够重现实验观察结果，即TPI与F-肌动蛋白的结合非常弱，并且随着离子强度的增加而迅速减弱。BD结果证实了实验观察结果，即结合程度随着离子强度的增加而降低，并且TPI与F-肌动蛋白的相互作用是弱非特异性的，甚至不存在相互作用。
