DIFFUSION-DRIVEN MECHANISMS OF PROTEIN TRANSLOCATION ON NUCLEIC-ACIDS .1. MODELS AND THEORY
DIFFUSION-DRIVEN MECHANISMS OF PROTEIN TRANSLOCATION ON NUCLEIC-ACIDS .1. MODELS AND THEORY
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DOI：
10.1021/bi00527a028
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发表时间：
1981-01-01
期刊：
影响因子：
2.9
通讯作者：
VONHIPPEL, PH
中科院分区：
文献类型：
--
作者：
BERG, OG;WINTER, RB;VONHIPPEL, PH
通过与特定的染色体目标碱基对序列(例如，操纵子或启动子)结合而发挥作用的基因组调节蛋白(例如，抑制子或聚合酶)似乎比扩散控制的速度更快地到达它们的目标。这些蛋白质对非特异性DNA也表现出明显的亲和力，因此这种明显促进的结合率必须按照两步结合机制来解释。第一步涉及自由扩散到DNA上的任何非特异性结合部位，第二步包括一系列蛋白质易位事件，这些事件也是由热波动驱动的。由于非特异性结合，第二步中的搜索过程是降维(或体积)的；这导致目标位置的表观速度加快。定义了四种类型的过程，它们可能参与这些DNA位点之间的蛋白质易位事件。这些是DNA分子结构域内的宏观解离-再解离过程，DNA分子中紧密位置之间的微观解离-再解离事件，DNA分子不同片段之间的链段间转移(通过环闭合)过程，以及沿着DNA分子滑动。给出了这些过程中每个过程的数学和物理描述，并计算出每个过程对总的靶定位速率的影响，作为蛋白质和DNA之间的非特异性结合亲和力和包含靶序列的DNA分子长度的函数。这一理论是根据大肠杆菌lac抑制子-操纵子的相互作用而发展的，因为测试这些方法的数据可用于该系统。这种方法对于分析生物靶标定位的机制是通用的，该机制涉及通过与靶标构成小部分的一般系统的非特异性结合来促进转移过程。
Genome regulatory proteins (e.g., repressors or polymerases) that function by binding to specific chromosomal target base pair sequences (e.g., operators or promoters) can appear to arrive at their targets at faster than diffusion-controlled rates. These proteins also exhibit appreciable affinity for nonspecific DNA, and thus this apparently facilitated binding rate must be interpreted in terms of a 2-step binding mechanism. The 1st step involves free diffusion to any nonspecific binding site on the DNA, and the 2nd step comprises a series of protein translocation events that are also driven by thermal fluctuations. Because of nonspecific binding, the search process in the 2nd step is of reduced dimensionality (or volume); this results in an accelerated apparent rate of target location. Four types of processes that may be involved in these protein translocation events between DNA sites are defined. These are macroscopic dissociation-reassociation processes within the domain of the DNA molecule, microscopic dissociation-reassociation events between closely spaced sites in the DNA molecule, intersegment transfer (via ring-closure) processes between different segments of the DNA molecule, and sliding along the DNA molecule. Mathematical and physical descriptions of each of these processes are presented, and the consequences of each for the overall rate of target location are worked out as a function of both the nonspecific binding affinity between protein and DNA and the length of the DNA molecule containing the target sequence. The theory is developed in terms of the Escherichia coli lac repressor-operator interaction since data for testing these approaches are available for this system. This approach is general for the analysis of mechanisms of biological target location involving facilitated transfer processes via nonspecific binding to the general system of which the target forms a small part.