Wessén Jonas, De La Cruz Nancy, Lyons Heankel, Chan Hue Sun, Sabari Benjamin R
Department of Biochemistry, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
These authors contributed equally to this work.
bioRxiv. 2025 Jun 18:2025.06.13.659429. doi: 10.1101/2025.06.13.659429.
While specificity of biomolecular interactions is typically understood to require interactions involving ordered structures, several biomolecular condensates exhibit specificity in the absence of apparent structural order. We have previously shown that condensates composed of the disordered region of MED1 partition specific proteins, mediated by sequence patterns of charged amino acids on the disordered regions of both MED1 and the interacting partner. Whether this specificity is due to an unknown ordered-structure-mediated interaction or from the dynamic multivalent interactions between the patterned charged amino acids in the disordered regions was unresolved. Here we show that a polymer physics-based model that only accounts for multivalent interactions among polymers in a statistical manner can largely explain published data on selective partitioning and make predictions that are subsequently experimentally validated. These results suggest that the specificity of condensate composition is underpinned to a substantial extent by multivalent interactions in the context of conformational disorder.
虽然人们通常认为生物分子相互作用的特异性需要涉及有序结构的相互作用，但一些生物分子凝聚物在没有明显结构秩序的情况下也表现出特异性。我们之前已经表明，由MED1无序区域组成的凝聚物会对特定蛋白质进行分区，这是由MED1和相互作用伙伴的无序区域上带电荷氨基酸的序列模式介导的。这种特异性是由于未知的有序结构介导的相互作用，还是由于无序区域中带图案的带电荷氨基酸之间的动态多价相互作用，尚未得到解决。在这里，我们表明，一个基于聚合物物理学的模型，该模型仅以统计方式考虑聚合物之间的多价相互作用，在很大程度上可以解释关于选择性分区的已发表数据，并做出随后经实验验证的预测。这些结果表明，凝聚物组成的特异性在很大程度上是由构象无序背景下的多价相互作用所支撑的。
