Capili A D, Schultz D C, RauscherIII F J, Borden K L
Structural Biology Program, Department of Physiology and Biophysics, Mount Sinai School of Medicine, New York University, New York, NY 10029, USA.
EMBO J. 2001 Jan 15;20(1-2):165-77. doi: 10.1093/emboj/20.1.165.
Plant homeodomain (PHD) domains are found in >400 eukaryotic proteins, many of which are transcriptional regulators. Naturally occurring point mutations or deletions of this domain contribute to a variety of human diseases, including ATRX syndrome, myeloid leukemias and autoimmune dysfunction. Here we report the first structural characterization of a PHD domain. Our studies reveal that the PHD domain from KAP-1 corepressor binds zinc in a cross-brace topology between anti-parallel ss-strands reminiscent of RING (really interesting new gene) domains. Using a mutational analysis, we define the structural features required for transcriptional repression by KAP-1 and explain naturally occurring, disease-causing mutations in PHD domains of other proteins. From a comparison of this PHD structure with previously reported RING and LIM (Lin11/Isl-1/Mec-3) structures, we infer sequence determinants that allow discrimination among PHD, RING and LIM motifs.
植物同源异型结构域（PHD）存在于400多种真核生物蛋白质中，其中许多是转录调节因子。该结构域的自然发生的点突变或缺失会导致多种人类疾病，包括ATRX综合征、髓系白血病和自身免疫功能障碍。在此，我们报道了PHD结构域的首个结构特征。我们的研究表明，来自KAP-1共抑制因子的PHD结构域在反平行单链之间以交叉支撑拓扑结构结合锌，这让人联想到RING（真核生物中一类具有重要调控功能的蛋白质家族）结构域。通过突变分析，我们确定了KAP-1转录抑制所需的结构特征，并解释了其他蛋白质PHD结构域中自然发生的致病突变。通过将这种PHD结构与先前报道的RING和LIM（Lin11/Isl-1/Mec-3）结构进行比较，我们推断出了能够区分PHD、RING和LIM基序的序列决定因素。
