不对称寡聚化状态和序列模式可以调节多相凝析相互溶性，这一成果由美国普林斯顿大学Clifford P. Brangwynne团队经过不懈努力而取得。2024年2月21日出版的《自然-化学》杂志发表了这项成果。

在该研究中，研究组通过体内凝析物重构实验和粗粒度分子模拟，来研究寡聚化和序列相互作用如何调节生物分子凝析物中的多相组织。课题组研究人员证明，增加一个内在无序蛋白的寡聚化状态导致增强的不混溶性和多相形成。

有趣的是，该课题组人员发现寡聚化以一种不对称的方式调节了内在无序蛋白的混溶性，当表现出更强的同型相互作用的内在无序蛋白被寡聚化时，这种效果更为明显。他们的研究结果表明，寡聚化是一种灵活的生物物理机制，细胞可以利用它来调节生物分子凝聚物的内部组织及其相关的生物学功能。

研究人员表示，内源性生物分子凝聚体由大量RNA和蛋白质组成，可以组成具有不同组成相的多相结构。这种多相组织通常被认为是促进其正常生物学功能的关键。然而，驱动多相形成的生物物理原理尚未完全理解。

附：英文原文

Title: Asymmetric oligomerization state and sequence patterning can tune multiphase condensate miscibility

Author: Rana, Ushnish, Xu, Ke, Narayanan, Amal, Walls, Mackenzie T., Panagiotopoulos, Athanassios Z., Avalos, Jos L., Brangwynne, Clifford P.

Issue&Volume: 2024-02-21

Abstract: Endogenous biomolecular condensates, composed of a multitude of proteins and RNAs, can organize into multiphasic structures with compositionally distinct phases. This multiphasic organization is generally understood to be critical for facilitating their proper biological function. However, the biophysical principles driving multiphase formation are not completely understood. Here we use in vivo condensate reconstitution experiments and coarse-grained molecular simulations to investigate how oligomerization and sequence interactions modulate multiphase organization in biomolecular condensates. We demonstrate that increasing the oligomerization state of an intrinsically disordered protein results in enhanced immiscibility and multiphase formation. Interestingly, we find that oligomerization tunes the miscibility of intrinsically disordered proteins in an asymmetric manner, with the effect being more pronounced when the intrinsically disordered protein, exhibiting stronger homotypic interactions, is oligomerized. Our findings suggest that oligomerization is a flexible biophysical mechanism that cells can exploit to tune the internal organization of biomolecular condensates and their associated biological functions.

DOI: 10.1038/s41557-024-01456-6

Source: https://www.nature.com/articles/s41557-024-01456-6