Vinson C R, Garcia K C
Laboratory of Biochemistry, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
New Biol. 1992 Apr;4(4):396-403.
The basic-helix-loop-helix-zipper (bHLH-Zip) motif is a conserved region of approximately 70 amino acids that mediates both sequence-specific DNA binding and protein dimerization. This motif is found in protein sequences from many eukaryotic organisms and is contained in the protein sequence of the oncogene myc and its partner max, and a shortened version of the motif (bHLH) is found in the muscle determination factor myoD and its partner E12. An evaluation of the conserved amino acids that define the motif coupled with the published mutagenic studies of this region has led to our formulation of a molecular model for the binding of this motif as a dimer to specific sequences of DNA. This model has the dimeric protein interacting with an abutted, dyad-symmetric DNA sequence. Helix 2 of each monomer is modeled as a coiled-coil extension of the C-terminal "leucine zipper." Helix 1 does not interact with helix 1 from its partner in the dimer but with the hydrophobic surface created when the helix 2 regions of the dimer interact with each other as a coiled-coil. Sequence-specific interactions are proposed between the basic region and the invariant cis elements that all bHLH-Zip proteins bind.
碱性螺旋-环-螺旋-拉链（bHLH-Zip）基序是一个约70个氨基酸的保守区域，它介导序列特异性DNA结合和蛋白质二聚化。该基序存在于许多真核生物的蛋白质序列中，包含在癌基因myc及其伙伴max的蛋白质序列中，并且在肌肉决定因子myoD及其伙伴E12中发现了该基序的一个缩短版本（bHLH）。对定义该基序的保守氨基酸的评估以及该区域已发表的诱变研究，促使我们构建了一个分子模型，用于解释该基序作为二聚体与特定DNA序列结合的过程。在这个模型中，二聚体蛋白质与相邻的、二元对称的DNA序列相互作用。每个单体的螺旋2被模拟为C端“亮氨酸拉链”的卷曲螺旋延伸。螺旋1在二聚体中不与其伙伴的螺旋1相互作用，而是与当二聚体的螺旋2区域作为卷曲螺旋相互作用时产生的疏水表面相互作用。推测碱性区域与所有bHLH-Zip蛋白结合的不变顺式元件之间存在序列特异性相互作用。
