SAIC-Frederick, Inc., NCI-Frederick, Maryland 21702, USA.
ACS Chem Biol. 2010 Mar 19;5(3):265-72. doi: 10.1021/cb900293a.
Studies of binding are often question: first, is the observed binding functional, and second, if it is, which function? Is it activation or repression? The first question relates to binding at different sites; the second relates to binding at similar sites. These questions apply to transcription factors binding to genomic DNA and to protein interaction domains binding to their partners. Here, we explain that both can be understood in terms of allostery and the cellular (or in vitro) environment. The idea is simple yet powerful; it emphasizes the role of allostery in defining whether binding between transcription factors and (cognate or noncognate) DNA sequences will lead to function and to the type of function. Allosteric effects are the outcome of dynamically shifting populations; thus binding to even slightly different DNA sequences will lead to different transcription factor conformations that can be reflected in the binding sites to their co-regulators. Currently, allostery is not considered when trying to understand how binding phenomena determine the functional outcome. Allosteric effects can enhance the binding specificity in a function-oriented manner. Here we provide a biological rationale that considers cellular crowding effects.
首先，观察到的结合是否具有功能？其次，如果具有功能，是哪种功能，是激活还是抑制？第一个问题涉及到不同结合位点的结合，第二个问题涉及到相似结合位点的结合。这些问题适用于与基因组 DNA 结合的转录因子，以及与它们的配体结合的蛋白质相互作用结构域。在这里，我们解释说，这两者都可以根据变构作用和细胞（或体外）环境来理解。这个想法简单而强大；它强调了变构作用在确定转录因子与（同源或非同源）DNA 序列之间的结合是否会导致功能以及功能类型方面的作用。变构效应是动态变化的群体的结果；因此，与稍微不同的 DNA 序列的结合将导致不同的转录因子构象，这可以反映在与其共调节剂的结合位点上。目前，在试图理解结合现象如何决定功能结果时，并没有考虑变构作用。变构效应可以以功能为导向增强结合特异性。在这里，我们提供了一个考虑细胞拥挤效应的生物学基本原理。
