Anbanandam Asokan, Albarado Diana C, Nguyen Catherine T, Halder Georg, Gao Xiaolian, Veeraraghavan Sudha
Department of Biochemistry & Molecular Biology, University of Texas Medical School, Houston, TX 77030, USA.
Proc Natl Acad Sci U S A. 2006 Nov 14;103(46):17225-30. doi: 10.1073/pnas.0607171103. Epub 2006 Nov 3.
Transcription enhancer factor 1 is essential for cardiac, skeletal, and smooth muscle development and uses its N-terminal TEA domain (TEAD) to bind M-CAT elements. Here, we present the first structure of TEAD and show that it is a three-helix bundle with a homeodomain fold. Structural data reveal how TEAD binds DNA. Using structure-function correlations, we find that the L1 loop is essential for cooperative loading of TEAD molecules on to tandemly duplicated M-CAT sites. Furthermore, using a microarray chip-based assay, we establish that known binding sites of the full-length protein are only a subset of DNA elements recognized by TEAD. Our results provide a model for understanding the regulation of genome-wide gene expression during development by TEA/ATTS family of transcription factors.
转录增强因子1对心脏、骨骼和平滑肌的发育至关重要，并利用其N端TEA结构域（TEAD）结合M-CAT元件。在此，我们展示了TEAD的首个结构，并表明它是一个具有同源异型域折叠的三螺旋束。结构数据揭示了TEAD如何结合DNA。利用结构-功能相关性，我们发现L1环对于TEAD分子协同加载到串联重复的M-CAT位点至关重要。此外，通过基于微阵列芯片的分析，我们确定全长蛋白的已知结合位点只是TEAD识别的DNA元件的一个子集。我们的结果为理解TEA/ATTS转录因子家族在发育过程中对全基因组基因表达的调控提供了一个模型。
