Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Carrer de Baldiri Reixac 10, Barcelona 08028, Spain; Department of Medicine and Life Sciences, Universitat Pompeu Fabra (MELIS-UPF), Carrer del Doctor Aiguader 88, Barcelona 08003, Spain.
Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Carrer de Baldiri Reixac 10, Barcelona 08028, Spain; Institució Catalana de Recerca i Estudis Avançats (ICREA), Passeig Lluís Companys 23, Barcelona 08010, Spain.
Curr Opin Struct Biol. 2024 Feb;84:102764. doi: 10.1016/j.sbi.2023.102764. Epub 2024 Jan 11.
A full understanding of protein structure is key to unraveling how these systems work, how mutations affect their function, and discovering new hotspots for drug discovery. Research tackling this field began with the analysis of globular proteins. In recent years, as technology has improved, research efforts have broadened their focus to include the study of multidomain proteins and the analysis of conformational variability, flexibility, and dynamic systems. Here, we have selected five recent examples that integrate complementary structural methods to provide insight into the behavior of modular, flexible, and transient contacts. We also describe the structural application of domains derived from single-chain antibodies, which are instrumental in overcoming the size limitation of cryogenic electron microscopy (cryoEM) studies. As these methods are continuously developed, they will lead to the interrogation of more complex systems, revealing how large signaling and transcriptional machines are assembled in the context of health and disease.
全面了解蛋白质结构是揭示这些系统如何工作、突变如何影响其功能以及发现新药物发现热点的关键。研究这一领域的工作始于对球状蛋白的分析。近年来，随着技术的进步，研究工作的重点已经扩大，包括研究多结构域蛋白和分析构象变异性、柔韧性和动态系统。在这里，我们选择了五个最近的例子，这些例子综合了互补的结构方法，为研究模块化、灵活和瞬态接触的行为提供了深入的了解。我们还描述了源自单链抗体的结构应用，这些抗体在克服低温电子显微镜（cryoEM）研究的大小限制方面发挥了重要作用。随着这些方法的不断发展，它们将导致对更复杂系统的研究，揭示在健康和疾病背景下，大型信号和转录机器是如何组装的。
