Department of Biomedical Engineering and Center for Biomolecular Condensates, Washington University in St. Louis, St. Louis, MO, USA.
Department of Structural Biology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Nat Commun. 2022 Dec 13;13(1):7722. doi: 10.1038/s41467-022-35370-7.
Biomolecular condensates form via coupled associative and segregative phase transitions of multivalent associative macromolecules. Phase separation coupled to percolation is one example of such transitions. Here, we characterize molecular and mesoscale structural descriptions of condensates formed by intrinsically disordered prion-like low complexity domains (PLCDs). These systems conform to sticker-and-spacers architectures. Stickers are cohesive motifs that drive associative interactions through reversible crosslinking and spacers affect the cooperativity of crosslinking and overall macromolecular solubility. Our computations reproduce experimentally measured sequence-specific phase behaviors of PLCDs. Within simulated condensates, networks of reversible inter-sticker crosslinks organize PLCDs into small-world topologies. The overall dimensions of PLCDs vary with spatial location, being most expanded at and preferring to be oriented perpendicular to the interface. Our results demonstrate that even simple condensates with one type of macromolecule feature inhomogeneous spatial organizations of molecules and interfacial features that likely prime them for biochemical activity.
生物分子凝聚体通过多价缔合大分子的偶联缔合和隔离相分离形成。与渗透相分离耦联的是这种转变的一个例子。在这里，我们描述了由固有无序的朊病毒样低复杂度域 (PLCD) 形成的凝聚体的分子和介观结构描述。这些系统符合贴纸和间隔物的结构。贴纸是通过可逆交联驱动缔合相互作用的内聚基序，而间隔物影响交联的协同性和整体大分子的溶解度。我们的计算再现了 PLCD 实验测量的序列特异性相行为。在模拟凝聚体中，可逆的间贴纸交联网络将 PLCD 组织成小世界拓扑。PLCD 的整体尺寸随空间位置而变化，在界面处最扩展并倾向于垂直取向。我们的结果表明，即使是具有一种类型大分子的简单凝聚体，也具有分子的不均匀空间组织和界面特征，这些特征可能为生化活性做好准备。
