Molecular recognition of the nucleosomal "supergroove"
Molecular recognition of the nucleosomal "supergroove"
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DOI：
10.1073/pnas.0401743101
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发表时间：
2004-05-04
影响因子：
11.1
通讯作者：
Luger, K
中科院分区：
文献类型：
--
作者：
Edayathumangalam, RS;Weyermann, P;Luger, K
染色质是真核生物DNA所有过程中的生理底物。通过将147个碱基对的DNA组织成两个紧密的超螺旋线圈，核小体产生了一种结构，在这种结构中，线性DNA上相隔80个碱基对的DNA区域靠得很近，从而形成了DNA“超级凹槽”。在这里，我们报告了一个发夹聚酰胺晚餐的设计，目标是一个这样的超级槽。核小体-聚酰胺复合物的2埃晶体结构表明，二价“夹子”有效地交联了DNA超螺旋的两个旋回，提高了DNA在组蛋白八聚体上的定位，并稳定了核小体的解离。我们的研究结果确定核小体超槽作为浓缩真核生物DNA分子识别的平台。在体内，超凹槽可以通过将两个调控元件并置来促进协同蛋白-蛋白相互作用。由于超槽的形成与DNA在组蛋白八聚体上的翻译位置无关，因此在参与真核基因调控的超槽中不需要精确的核小体定位。
Chromatin is the physiological substrate in all processes involving eukaryotic DNA. By organizing 147 base pairs of DNA into two tight superhelical coils, the nucleosome generates an architecture where DNA regions that are 80 base pairs apart on linear DNA are brought into close proximity, resulting in the formation of DNA "supergrooves." Here, we report the design of a hairpin polyamide dinner that targets one such supergroove. The 2-Angstrom crystal structure of the nucleosome-polyamide complex shows that the bivalent "clamp" effectively crosslinks the two gyres of the DNA superhelix, improves positioning of the DNA on the histone octamer, and stabilizes the nucleosome against dissociation. Our findings identify nucleosomal supergrooves as platforms for molecular recognition of condensed eukaryotic DNA. In vivo, supergrooves may foster synergistic protein-protein interactions by bringing two regulatory elements into juxtaposition. Because supergroove formation is independent of the translational position of the DNA on the histone octamer, accurate nucleosome positioning over regulatory elements is not required for supergroove participation in eukaryotic gene regulation.