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首页> 外文期刊>Journal of Molecular Biology >Structural analysis of HMGD-DNA complexes reveals influence of intercalation on sequence selectivity and DNA bending.
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Structural analysis of HMGD-DNA complexes reveals influence of intercalation on sequence selectivity and DNA bending.

机译：HMGD-DNA复合物的结构分析揭示了插入对序列选择性和DNA弯曲的影响。

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摘要

The ubiquitous, eukaryotic, high-mobility group box (HMGB) chromosomal proteins promote many chromatin-mediated cellular activities through their non-sequence-specific binding and bending of DNA. Minor-groove DNA binding by the HMG box results in substantial DNA bending toward the major groove owing to electrostatic interactions, shape complementarity, and DNA intercalation that occurs at two sites. Here, the structures of the complexes formed with DNA by a partially DNA intercalation-deficient mutant of Drosophila melanogaster HMGD have been determined by X-ray crystallography at a resolution of 2.85 A. The six proteins and 50 bp of DNA in the crystal structure revealed a variety of bound conformations. All of the proteins bound in the minor groove, bridging DNA molecules, presumably because these DNA regions are easily deformed. The loss of the primary site of DNA intercalation decreased overall DNA bending and shape complementarity. However, DNA bending at the secondary site of intercalation was retained and most protein-DNA contacts were preserved. The mode of binding resembles the HMGB1 box A-cisplatin-DNA complex, which also lacks a primary intercalating residue. This study provides new insights into the binding mechanisms used by HMG boxes to recognize varied DNA structures and sequences as well as modulate DNA structure and DNA bending.
机译：普遍存在的真核生物高迁移率族盒（HMGB）染色体蛋白通过它们的非序列特异性结合和DNA弯曲促进了许多染色质介导的细胞活性。由于静电相互作用，形状互补性和在两个位置发生的DNA嵌入，HMG盒结合的小沟槽DNA导致大量DNA向着主要凹槽弯曲。在这里，已通过X射线晶体学测定了果蝇果蝇HMGD的部分DNA插入缺陷型突变体与DNA形成的复合物的结构。在晶体结构中显示了6种蛋白质和50 bp DNA各种结合构象。所有蛋白质都结合在小沟中，桥接DNA分子，大概是因为这些DNA区域容易变形。 DNA插入的主要位点的丢失减少了总体DNA弯曲和形状互补性。但是，保留了在插入的次要部位弯曲的DNA，并保留了大多数蛋白质与DNA的接触。结合方式类似于HMGB1盒A-顺铂-DNA复合物，该复合物也缺少主要的插入残基。这项研究为HMG盒用于识别各种DNA结构和序列以及调节DNA结构和DNA弯曲的结合机制提供了新见解。

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