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引用次数: 0
摘要
基因表达调控既需要多样性,也需要特异性。如何协调这两个相互矛盾的条件?动态的 DNA 识别机制会导致异质的结合构象,而这些构象会因细胞线索而改变。在此,我们总结了最近的实验证据,说明模糊相互作用如何有助于染色质重塑、DNA 复制和修复调控以及转录因子结合。我们描述了 DNA 与调控因子之间的结合模式连续性如何导致可变的多位点接触模式、多电解质竞争、即时形状读数、由翻译后修饰或动态寡聚机制控制的自动抑制。越来越多的实验证据支持结合蛋白质-DNA 组装的崎岖能量景观,对其进行调节可导致不同的功能结果。最近的研究结果表明,这些组合机制在进化过程中保持了可塑性转录机制中适度的序列限制。
Fuzzy protein-DNA interactions and beyond: A common theme in transcription?
Gene expression regulation requires both diversity and specificity. How can these two contradictory conditions be reconciled? Dynamic DNA recognition mechanisms lead to heterogeneous bound conformations, which can be shifted by the cellular cues. Here we summarise recent experimental evidence on how fuzzy interactions contribute to chromatin remodelling, regulation of DNA replication and repair and transcription factor binding. We describe how the binding mode continuum between DNA and regulatory factors lead to variable, multisite contact patterns; polyelectrolyte competitions; on-the-fly shape readouts; autoinhibition controlled by posttranslational modifications or dynamic oligomerisation mechanisms. Increasing experimental evidence supports the rugged energy landscape of the bound protein-DNA assembly, modulation of which leads to distinct functional outcomes. Recent results suggest the evolutionary conservation of these combinatorial mechanisms with moderate sequence constraints in the malleable transcriptional machinery.
期刊介绍:
Current Opinion in Structural Biology (COSB) aims to stimulate scientifically grounded, interdisciplinary, multi-scale debate and exchange of ideas. It contains polished, concise and timely reviews and opinions, with particular emphasis on those articles published in the past two years. In addition to describing recent trends, the authors are encouraged to give their subjective opinion of the topics discussed.
In COSB, we help the reader by providing in a systematic manner:
1. The views of experts on current advances in their field in a clear and readable form.
2. Evaluations of the most interesting papers, annotated by experts, from the great wealth of original publications.
[...]
The subject of Structural Biology is divided into twelve themed sections, each of which is reviewed once a year. Each issue contains two sections, and the amount of space devoted to each section is related to its importance.
-Folding and Binding-
Nucleic acids and their protein complexes-
Macromolecular Machines-
Theory and Simulation-
Sequences and Topology-
New constructs and expression of proteins-
Membranes-
Engineering and Design-
Carbohydrate-protein interactions and glycosylation-
Biophysical and molecular biological methods-
Multi-protein assemblies in signalling-
Catalysis and Regulation