the stability of a stochastic camkii switch dependence on the number of enzyme molecules and protein turnover一个随机camkii开关的稳定性依赖酶分子和蛋白质周转的次数.pdfVIP

Open access, freely available online PLoS BIOLOGY The Stability of a Stochastic CaMKII Switch: Dependence on the Number of Enzyme Molecules and Protein Turnover Paul Miller1,2, Anatol M. Zhabotinsky1,3, John E. Lisman1,4, Xiao-Jing Wang1,2* 1 Volen Center for Complex Systems, Brandeis University, Waltham, Massachusetts, United States of America, 2 Department of Physics, Brandeis University, Waltham, Massachusetts, United States of America, 3 Department of Chemistry, Brandeis University, Waltham, Massachusetts, United States of America, 4 Department of Biology, Brandeis University, Waltham, Massachusetts, United States of America Molecular switches have been implicated in the storage of information in biological systems. For small structures such as synapses, these switches are composed of only a few molecules and stochastic fluctuations are therefore of importance. Such fluctuations could potentially lead to spontaneous switch reset that would limit the lifetime of information storage. We have analyzed a model of the calcium/calmodulin-dependent protein kinase II (CaMKII) switch implicated in long-term memory in the nervous system. The bistability of this switch arises from autocatalytic autophosphorylation of CaMKII, a reaction that is countered by a saturable phosphatase-1-mediated dephosphor- ylation. We sought to understand the factors that control switch stability and to determine the functional relationship between stability and the number of molecules involved. Using Monte Carlo simulations, we found that the lifetime of states of the switch increase exponentially with the number of CaMKII holoenzymes. Switch stability requires a balance between the kinase and phosphatase rates, and the kinase rate mus