The SAND domain structure defines a novel DNA-binding fold in transcriptional regulation
The SAND domain structure defines a novel DNA-binding fold in transcriptional regulation
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DOI：
10.1038/89675
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发表时间：
2001-07-01
期刊：
影响因子：
--
通讯作者：
Sattler, M
中科院分区：
文献类型：
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作者：
Bottomley, MJ;Collard, MW;Sattler, M
SAND 结构域是在许多核蛋白中发现的保守序列基序，包括 Sp100 家族和 NUDR。这些被认为在染色质依赖性转录调控中发挥重要作用，并与许多疾病有关。我们已经从 Sp100b 确定了 SAND 域的三维 (3D) 结构。该结构代表了一种新的α/β折叠，其中在α螺旋、带正电荷的表面斑块内发现了保守的KDWK序列基序。对于 NUDR，SAND 结构域足以介导 DNA 结合。通过突变分析和化学位移扰动实验，DNA 结合表面被映射到包含 KDWK 基序的 a 螺旋区域。野生型和突变蛋白的体外 DNA 结合活性与体内全长 NUDR 的转录调控活性相关。进化上保守的 SAND 结构域定义了一种新的 DNA 结合折叠，参与染色质相关转录调控。
The SAND domain is a conserved sequence motif found in a number of nuclear proteins, including the Sp100 family and NUDR. These are thought to play important roles in chromatin-dependent transcriptional regulation and are linked to many diseases. We have determined the three-dimensional (3D) structure of the SAND domain from Sp100b. The structure represents a novel alpha/beta fold, in which a conserved KDWK sequence motif is found within an a-helical, positively charged surface patch. For NUDR, the SAND domain is shown to be sufficient to mediate DNA binding. Using mutational analyses and chemical shift perturbation experiments, the DNA binding surface is mapped to the a-helical region encompassing the KDWK motif. The DNA binding activity of wild type and mutant proteins in vitro correlates with transcriptional regulation activity of full length NUDR in vivo. The evolutionarily conserved SAND domain defines a new DNA binding fold that is involved in chromatin-associated transcriptional regulation.