Peking University made a breakthrough in protoplast dynamic analysis

Medical Network November 19th, November 12th, State Key Laboratory of Artificial Microstructures and Mesoscopic Physics, School of Physics, Peking University, Mao Yuandong, Research Center for Quantitative Biology, Frontier Interdisciplinary Group, published online in Nature A research paper entitled Cryo-EM structures and dynamics of substrate-engaged human 26S proteasome ("Frozen Electron Structure and Kinetics of Substrate-bound Human 26S Proteasome"). According to reports, this is the first paper published in the journal Nature, which is superior to the 3.6 angstrom resolution level experimental study of the dynamic process and principle of the super-complex protein machine, marking the development of cryo-electron microscopy has finally begun to look forward to The long-standing new era of all-atom dynamics analysis has been praised by reviewers as a “milestone” in related fields.

It is reported that since the editorial and reviewers of Nature have attached great importance to the paper, the paper was submitted from September 11th this year to the official website on November 12th. It took only two months to speed up the publication. The form is published online.

Ubiquitin-Proteasome System (UPS) is the most important protein degradation pathway in cells, which maintains the concentration balance of proteins in organisms and the rapid degradation of proteins that regulate proteins, misfolded or damaged proteins. It plays a vital role in various cell processes such as cell cycle and gene expression regulation. Protein metabolism abnormalities caused by UPS malfunction are directly related to many major human diseases .

Although the above work reveals the basic architecture and intrinsic motor behavior of the proteasome, due to the lack of interaction between the proteasome and the substrate, there is no known about the atomic-level working mechanism of how the proteasome achieves substrate degradation. In addition, although cryo-electron microscopy has been widely used in recent years to analyze protein complex structures and equilibrium conformations with dynamic characteristics, the resolution levels of intermediate structure and non-equilibrium conformation analysis are often limited to 4-6 angstroms or less. There is still a considerable distance from the true all-atom level dynamics analysis.

The paper, through the combination of cryo-electron microscopy and machine learning techniques, analyzes the high-resolution (2.8-3.6 angstrom) fine atomic structure of the seven intermediate-state conformations of human proteasome 26S in the process of degradation of the substrate, preferably local resolution. The rate is 2.5 angstroms.

According to Peking University, these findings provide valuable first-hand atomic structure and kinetic information for decades of research on proteasome function, understanding the degradation process of proteins in organisms and a series of ATPase motors responsible for substance transport. The general working principle of the molecule has extremely important scientific significance, and it also marks the construction of the cryo-electron microscope platform of Peking University. It has reached the international leading level in data collection efficiency and imaging resolution.