Program in Chemistry and Chemical Biology, University of California, San Francisco, United States; Department of Pharmaceutical Chemistry, University of California, San Francisco, United States.
Program in Chemistry and Chemical Biology, University of California, San Francisco, United States; Department of Pharmaceutical Chemistry, University of California, San Francisco, United States.
J Magn Reson. 2023 Jan;346:107318. doi: 10.1016/j.jmr.2022.107318.
Diverse cellular processes have been observed or predicted to occur in biomolecular condensates, which are comprised of proteins and nucleic acids that undergo liquid-liquid phase separation (LLPS). Protein-driven LLPS often involves weak, multivalent interactions between intrinsically disordered regions (IDRs). Due to their inherent lack of defined tertiary structures, NMR has been a powerful resource for studying the behavior and interactions of IDRs in condensates. While IDRs in proteins are necessary for phase separation, core proteins enriched in condensates often contain structured domains that are essential for their function and contribute to phase separation. How phase separation can affect the structure and conformational dynamics of structured domains is critical for understanding how biochemical reactions can be effectively regulated in cellular condensates. In this perspective, we discuss the consequences phase separation can have on structured domains and outline NMR observables we believe are useful for assessing protein structure and dynamics in condensates.
多种细胞过程已被观察或预测发生在生物分子凝聚物中，这些凝聚物由经历液-液相分离（LLPS）的蛋白质和核酸组成。由蛋白质驱动的 LLPS 通常涉及固有无序区域（IDR）之间的弱、多价相互作用。由于其固有的缺乏明确的三级结构，NMR 一直是研究凝聚物中 IDR 行为和相互作用的强大资源。虽然蛋白质中的 IDR 对于相分离是必要的，但富含凝聚物的核心蛋白质通常含有结构域，这些结构域对于它们的功能至关重要，并有助于相分离。相分离如何影响结构域的结构和构象动力学对于理解生物化学反应如何在细胞凝聚物中得到有效调节至关重要。在这篇观点文章中，我们讨论了相分离对结构域的可能影响，并概述了我们认为有助于评估凝聚物中蛋白质结构和动力学的 NMR 可观测结果。
