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Abstract：
Communication within cells relies on a few protein nodes called hubs, which organize vast interactomes with many partners. Frequently, hub proteins are intrinsically disordered conferring multi-specificity and dynamic communication. Conversely, folded hub proteins may organize networks using disordered partners. In this work, the structure of the RST domain, a unique folded hub, is solved by nuclear magnetic resonance spectroscopy and small-angle X-ray scattering, and its complex with a region of the transcription factor DREB2A is provided through data-driven HADDOCK modeling and mutagenesis analysis. The RST fold is unique, but similar structures are identified in the PAH (paired amphipathic helix), TAFH (TATA-box-associated factor homology), and NCBD (nuclear coactivator binding domain) domains. We designate them as a group the αα hubs, as they share an αα-hairpin super-secondary motif, which serves as an organizing platform for malleable helices of varying topology. This allows for partner adaptation, exclusion, and selection. Our findings provide valuable insights into structural features enabling signaling fidelity.
摘要：
细胞内的通讯依赖于一些称为集线器的蛋白质节点，与许多合作伙伴组织了大量的互动。经常,hub蛋白本质上是无序的，赋予多特异性和动态通信。相反，折叠的hub蛋白可能使用无序的伙伴组织网络。在这项工作中,RST域的结构，一个独特的折叠轮毂，通过核磁共振波谱和小角度X射线散射来解决，通过数据驱动的HADDOCK建模和诱变分析提供了其与转录因子DREB2A区域的复合物。RST折叠是独一无二的，但在PAH（配对两亲性螺旋）中发现了类似的结构，TAFH（TATA盒相关因子同源性），和NCBD(核共激活子结合域)域。我们将它们指定为一组αα集线器，因为它们共享一个αα-发夹超次要基序，它可以作为不同拓扑结构的可延展螺旋的组织平台。这允许合作伙伴适应，排除,和选择。我们的发现为实现信号保真度的结构特征提供了有价值的见解。
