Division of Biomedical Measurements and Diagnostics, Graduate School of Biomedical Engineering, Tohoku University, Sendai, Japan.
Pharmaceutical Discovery Research Laboratories, Teijin Pharma Limited, Tokyo, Japan.
FEBS Lett. 2022 Jun;596(12):1576-1585. doi: 10.1002/1873-3468.14338. Epub 2022 Mar 27.
The function of the transcription factor BACH1 is regulated by heme binding to multiple Cys-Pro (CP) motifs within its intrinsically disordered regions. Here, biochemical analyses were conducted to reveal the individual functional roles of the CP motifs. Our findings revealed that four CP motifs in BACH1 individually contributed to the regulation of BACH1 activity by accepting heme in a five- and six-coordination manner. The model structure around the bZip domain indicated that the CP motifs are in the N- and C-terminal heme-binding regions, which are approximately 9 nm apart, suggesting that spatial location is important for the individual function of the CP motifs. The presence of multiple CP motifs with distinct roles may ensure the multifaceted, strict regulation of BACH1 by heme.
转录因子 BACH1 的功能受到其无规卷曲区域内多个 Cys-Pro (CP) 基序与血红素结合的调节。在此，通过生化分析揭示了 CP 基序的个体功能作用。我们的研究结果表明，BACH1 中的四个 CP 基序分别以五配位和六配位的方式接受血红素，从而调节 BACH1 的活性。围绕 bZip 结构域的模型结构表明，CP 基序位于 N-和 C-末端血红素结合区域，两者相距约 9nm，这表明空间位置对于 CP 基序的个体功能很重要。具有不同作用的多个 CP 基序的存在可能确保了血红素对 BACH1 的多方面、严格调节。
