Peking University has made a breakthrough in the analysis of protease body full atomic dynamics

November 12, the Mao Youdong Task Force of the National Key Laboratory of Artificial Microstructification and Mesophysics of Peking University's School of Physics, and the Center for Quantitative Biology of frontier cross-colleges, published a research paper online in the journal Nature entitled Cryo-EM Structures and Dynamics of substrate-engaged human 26S proteasome (Frozen electroscopic structure and dynamics of human source 26S proteases combined with bottoms). According to the introduction, this is the "nature" published in the systematic, better than the 3.6 E resolution level experimental study of the super-large composite protein machine dynamics process and principles of the first paper, marking the development of frozen electron mirror finally began to enter the long-awaited new era of all-atomic dynamics analysis, the reviewer praised as a related field of "milestone."
it is understood that due to the nature of the editorial department and reviewers of the paper published extremely important, the paper from September 11 this year to November 12 officially online, only two months, in the form of accelerated publication online.
Ubiquitin-Proteasome System (UPS) is the most important protein degradation pathline in cells, which plays an important role in maintaining the concentration balance of proteins in organisms, as well as the rapid degradation of proteins that regulate proteins, misfolded or damaged proteins, and is involved in cell cycles, gene expression regulation and other cellular processes, and protein metabolic abnormalities caused by UPS abnormalities are directly related to many major human diseases.
Although the above work reveals the basic structure and internal motor behavior of proteases, due to the lack of interaction between proteases and substrates, there is still no understanding of how proteases work at atomic levels to degrade substrates. In addition, although cryomirror technology has been widely used in recent years to analyze protein complex structure and equilibrium state composition with dynamic characteristics, the resolution level of its intermediate structure and non-equilibrium composition analysis is often limited to 4 to 6 E or lower, and there is still a considerable distance from the real all-atomic horizontal dynamics analysis.
And through the combination of frozen electron microscope and machine learning technology, the paper analyzes the high-resolution (2.8 to 3.6 E) fine atomic structure of 7 intermediate-state configurations in the process of degradation of human-origin protease 26S, preferably with a local resolution of 2.5 E.
according to Peking University, these results provide valuable first-hand atomic structure and dynamic information for decades of research on protease function, are of great scientific significance for understanding the degradation process of proteins in organisms and the general working principles of a series of ATPase motor molecules responsible for material transport, and also mark the construction of the freezing electron mirror platform of Peking University, which has reached the international leading level in data acquisition efficiency and imaging resolution. (China Youth Daily)