Nearest-neighbor non-additivity versus long-range non-additivity in TATA-box structure and its implications for TBP-binding mechanism
Nearest-neighbor non-additivity versus long-range non-additivity in TATA-box structure and its implications for TBP-binding mechanism
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DOI：
10.1093/nar/gkm451
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发表时间：
2007-01-01
影响因子：
14.9
通讯作者：
Haran, Tali E.
中科院分区：
文献类型：
--
作者：
Faiger, Hana;Ivanchenko, Marina;Haran, Tali E.
TBP通过识别其序列依赖的结构和灵活性来识别其目标位点TATA盒。研究这种被称为“间接读出”的TATA盒识别模式，对于阐明该系统中的结合机制以及开发在基因组DNA中定位新的结合位点的方法具有重要意义。我们测定了类共识TATA盒的结合稳定性和TBP诱导的TATA盒弯曲。此外，我们还计算了所有研究序列的个体信息得分。我们发现，塔塔盒子中存在各种非加性效应，这取决于它们的结构性质。根据几个标准，我们将塔塔盒子分为两大类。第一组包含3-4个连续腺嘌呤的序列。这个组中的序列具有严格的上下文无关的合作结构，最好地用最近邻非加性模型来描述。第二组中的序列具有灵活的、上下文相关的构象，这不能用加法模型或最近邻非加法模型来描述。根据这些和其他结构规则对TATA盒进行分类，阐明了TBP在与不同的TATA盒结合时使用的不同识别途径和结合机制。我们讨论了在间接读数占主导地位的蛋白质的概率权重矩阵法预测新结合位点困难的结构和进化来源。
TBP recognizes its target sites, TATA boxes, by recognizing their sequence-dependent structure and flexibility. Studying this mode of TATA-box recognition, termed 'indirect readout', is important for elucidating the binding mechanism in this system, as well as for developing methods to locate new binding sites in genomic DNA. We determined the binding stability and TBP-induced TATA-box bending for consensus-like TATA boxes. In addition, we calculated the individual information score of all studied sequences. We show that various non-additive effects exist in TATA boxes, dependent on their structural properties. By several criterions, we divide TATA boxes to two main groups. The first group contains sequences with 3-4 consecutive adenines. Sequences in this group have a rigid context-independent cooperative structure, best described by a nearest-neighbor non-additive model. Sequences in the second group have a flexible, context-dependent conformation, which cannot be described by an additive model or by a nearest-neighbor non-additive model. Classifying TATA boxes by these and other structural rules clarifies the different recognition pathways and binding mechanisms used by TBP upon binding to different TATA boxes. We discuss the structural and evolutionary sources of the difficulties in predicting new binding sites by probabilistic weight-matrix methods for proteins in which indirect readout is dominant.