Fisher D E, Carr C S, Parent L A, Sharp P A
Center for Cancer Research, Massachusetts Institute of Technology, Cambridge 02139.
Genes Dev. 1991 Dec;5(12A):2342-52. doi: 10.1101/gad.5.12a.2342.
The DNA-binding factor TFEB contains adjacent helix-loop-helix (HLH) and leucine zipper (LZ) domains flanked by an upstream basic region. This arrangement of interactive motifs has recently been observed in several other transcription factors and in the Myc family of oncogenes. TFEB was isolated by virtue of its binding to the major late promoter of adenovirus. DNA binding by a soluble protein was achieved by deleting a hydrophobic amino-terminal domain and permitted the structural analysis of the oligomerization and DNA-binding properties of TFEB. TFEB specifically bound DNA as both a homodimer and a heterodimer with another b-HLH-LZ protein TFE3. The LZ domain was essential for homo- or hetero-oligomerization and high-affinity DNA binding. In the absence of DNA a tetramer-sized form of TFEB was observed that dissociates to bind added DNA as a dimer. Binding by TFEB and TFE3 to related, but different, naturally occurring DNA target sequences was observed with distinct binding preferences. Analysis of basic domain residues in this family of proteins revealed a pattern of sequence conservation predictive of an interacting alpha-helical face. Common oligomerization and DNA-binding features suggest the b-HLH-LZ domain structure to define a distinct family of DNA-binding factors.
DNA结合因子TFEB包含相邻的螺旋-环-螺旋（HLH）和亮氨酸拉链（LZ）结构域，其侧翼为上游碱性区域。这种相互作用基序的排列最近在其他几种转录因子和致癌基因的Myc家族中也有观察到。TFEB是因其与腺病毒主要晚期启动子的结合而被分离出来的。通过缺失一个疏水氨基末端结构域实现了可溶性蛋白与DNA的结合，并对TFEB的寡聚化和DNA结合特性进行了结构分析。TFEB作为同二聚体和与另一种b-HLH-LZ蛋白TFE3的异二聚体特异性结合DNA。LZ结构域对于同型或异型寡聚化以及高亲和力DNA结合至关重要。在没有DNA的情况下，观察到一种四聚体大小的TFEB形式，它会解离以作为二聚体结合添加的DNA。观察到TFEB和TFE3与相关但不同的天然存在的DNA靶序列结合，具有不同的结合偏好。对该蛋白家族碱性结构域残基的分析揭示了一种序列保守模式，可预测相互作用的α-螺旋面。共同的寡聚化和DNA结合特征表明b-HLH-LZ结构域结构定义了一个独特的DNA结合因子家族。
