Dresden Courtney E, Andrianova Ekaterina P, Smith Brian J, Callery Nicole I, Kolonay Dominic, Holub Ashton S, Camacho Ricardo Urquidi, Choudury Sarah G, Higgins Isabella J, Zhulin Igor B, Husbands Aman Y
Department of Biology, University of Pennsylvania, 415 S. University Ave, Philadelphia, PA, 19104, USA.
Molecular, Cellular, and Developmental Biology, the Ohio State University, Columbus, OH 43215, USA.
bioRxiv. 2025 Aug 1:2025.07.29.667167. doi: 10.1101/2025.07.29.667167.
Transcription factors (TFs) integrate a diverse array of inputs to achieve the exquisite control of gene expression necessary for life. In plants, this is exemplified by the deeply conserved CLASS III HOMEODOMAIN LEUCINE ZIPPER (HD-ZIPIII) family of TFs. HD-ZIPIII activity is controlled by inputs at transcriptional, post-transcriptional, and post-translational levels. As part of their multidomain architecture, HD-ZIPIII TFs contain a StAR-related lipid transfer (START) domain, a ubiquitously distributed evolutionary module that binds various types of lipophilic ligands. Here, we show that HD-ZIPIII and HD-ZIPIV proteins contain a cryptic, deeply conserved START domain which we term the disorder-containing START domain (dSTART). The dSTART domain is required for HD-ZIPIII developmental function, controlling their subcellular localization and DNA-binding properties. The dSTART domain also helps discriminate responsive from non-responsive binding sites across the HD-ZIPIII shared genetic network. Finally, we identify candidate ligands of the dSTART domain including several species of phosphatidylglycerol and phosphatidic acid. The identification and functional characterization of a cryptic START domain provides new mechanistic insights into a deeply conserved family of TFs with roles in nearly all aspects of plant development.
转录因子（TFs）整合了各种各样的输入信号，以实现对生命所必需的基因表达的精确控制。在植物中，这一点在深度保守的III类同源结构域亮氨酸拉链（HD-ZIPIII）转录因子家族中得到了体现。HD-ZIPIII的活性受到转录、转录后和翻译后水平的输入信号的控制。作为其多结构域架构的一部分，HD-ZIPIII转录因子包含一个与类固醇生成急性调节蛋白（StAR）相关的脂质转移（START）结构域，这是一个广泛分布的进化模块，可结合各种类型的亲脂性配体。在这里，我们表明HD-ZIPIII和HD-ZIPIV蛋白含有一个隐秘的、深度保守的START结构域，我们将其称为含无序结构域的START结构域（dSTART）。dSTART结构域是HD-ZIPIII发育功能所必需的，它控制着它们的亚细胞定位和DNA结合特性。dSTART结构域还有助于区分HD-ZIPIII共享遗传网络中响应性和非响应性结合位点。最后，我们鉴定了dSTART结构域的候选配体，包括几种磷脂酰甘油和磷脂酸。一个隐秘的START结构域的鉴定和功能表征为一个在植物发育几乎所有方面都发挥作用且深度保守的转录因子家族提供了新的机制见解。
