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蛋白质-DNA光交联揭示转录复合物形成过程中的结构灵活性

Structural flexibility in transcription complex formation revealed by protein-DNA photocrosslinking.

作者信息

Cleary M A, Pendergrast P S, Herr W

机构信息

Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.

出版信息

Proc Natl Acad Sci U S A. 1997 Aug 5;94(16):8450-5. doi: 10.1073/pnas.94.16.8450.

DOI:10.1073/pnas.94.16.8450
PMID:9237997
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC22952/
Abstract

The Oct-1 POU domain binds diverse DNA-sequence elements and forms a higher-order regulatory complex with the herpes simplex virus coregulator VP16. The POU domain contains two separate DNA-binding domains joined by a flexible linker. By protein-DNA photocrosslinking we show that the relative positioning of the two POU DNA-binding domains on DNA varies depending on the nature of the DNA target. On a single VP16-responsive element, the POU domain adopts multiple conformations. To determine the structure of the Oct-1 POU domain in a multiprotein complex with VP16, we allowed VP16 to interact with previously crosslinked POU-domain-DNA complexes and found that VP16 can associate with multiple POU-domain conformations. These results reveal the dynamic potential of a DNA-binding domain in directing transcriptional regulatory complex formation.

摘要

Oct-1 POU结构域可结合多种DNA序列元件,并与单纯疱疹病毒共调节因子VP16形成高级调控复合物。POU结构域包含两个由柔性接头连接的独立DNA结合结构域。通过蛋白质-DNA光交联,我们发现两个POU DNA结合结构域在DNA上的相对定位因DNA靶标的性质而异。在单个VP16反应元件上,POU结构域呈现多种构象。为了确定Oct-1 POU结构域在与VP16形成的多蛋白复合物中的结构,我们让VP16与先前交联的POU结构域-DNA复合物相互作用,发现VP16可以与多种POU结构域构象结合。这些结果揭示了DNA结合结构域在指导转录调控复合物形成中的动态潜力。

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Structural flexibility in transcription complex formation revealed by protein-DNA photocrosslinking.蛋白质-DNA光交联揭示转录复合物形成过程中的结构灵活性
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本文引用的文献

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Structure of Pit-1 POU domain bound to DNA as a dimer: unexpected arrangement and flexibility.作为二聚体与DNA结合的Pit-1 POU结构域的结构:意外的排列和灵活性。
Genes Dev. 1997 Jan 15;11(2):198-212. doi: 10.1101/gad.11.2.198.
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Conformational alteration of Oct-1 upon DNA binding dictates selectivity in differential interactions with related transcriptional coactivators.Oct-1与DNA结合后发生的构象改变决定了其与相关转录共激活因子差异相互作用中的选择性。
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The VP16 accessory protein HCF is a family of polypeptides processed from a large precursor protein.病毒蛋白16辅助蛋白HCF是一类从大型前体蛋白加工而来的多肽家族。
Cell. 1993 Jul 16;74(1):115-25. doi: 10.1016/0092-8674(93)90299-6.
5
Spacing and orientation of bipartite DNA-binding motifs as potential functional determinants for POU domain factors.二分DNA结合基序的间距和方向作为POU结构域因子的潜在功能决定因素。
Genes Dev. 1993 Dec;7(12B):2483-96. doi: 10.1101/gad.7.12b.2483.
6
Crystal structure of the Oct-1 POU domain bound to an octamer site: DNA recognition with tethered DNA-binding modules.与八聚体位点结合的Oct-1 POU结构域的晶体结构:通过连接的DNA结合模块进行DNA识别。
Cell. 1994 Apr 8;77(1):21-32. doi: 10.1016/0092-8674(94)90231-3.
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Cell. 1994 Dec 2;79(5):841-52. doi: 10.1016/0092-8674(94)90073-6.
8
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Analysis of homeodomain function by structure-based design of a transcription factor.通过基于结构的转录因子设计对同源结构域功能进行分析。
Proc Natl Acad Sci U S A. 1995 Oct 10;92(21):9752-6. doi: 10.1073/pnas.92.21.9752.