On August 12, 2014, the Associate Professor Wei Zhiyi of Department of Biology of SUSTC cooperated with the research fellow of the Institute of Biophysics, Chinese Academy of Sciences Wang Yanli et. al to release a research paper named Crystal structure of the RNA-guided immune surveillance Cascade complex in Escherichia coli online in the magazine Nature of the U.K. , which described research progress of structural biology of key molecular machines in the immune system of procaryotic organism. The first author of the paper is the doctoral student Zhao Hongtu of Wang Yanli’s research group, and Associate Professor Wei Zhiyi and the researcher Wang Yanli are corresponding authors of the paper.

Although it is the original and simple life forms, the prokaryotic organism, including bacteria and archaea, like the human body, can resist immune system of the intruder, simple but efficient. The acquired immune system extensively existing in prokaryotic organism is composed of CRISPR RNA (crRNA) and multiple related proteins of CRISPR (Cas) , and can recognize and decompose genome of the intrusion virus. In E. Coil, such an immune system depends on forming of compound called Cascade. Cascade is assembled by 11 protein-based CasA1B2C6D1E1 along crRNA, and is a giant nuclear acid-protein compound with molecular weight of 405kDa. Due to high-resolution structure information available, assembling of Cascade and molecular mechanism recognizing external DNA are still unknown.

To solve the international difficulty, Associate Professor Wei Zhiyi and Institute of Biophysics, Chinese Academy of Science cooperated and analyzed high-resolution crystal structure with X-ray crystallography, and revealed fine 3D structure of the compound for the first time. The structure analysis discovers that, 8 sub-gene combination of crRNA and CasC/D/E form a curve structure layer, through interaction of these sub-genes, and crRNA forms a unique petal 3D structure to recognize specificity of external DNA. The 2^nd curve structure layer formed by CasA/B incurs conformation change when Cascade combines external DNA to assist crRNA in recognizing DNA. The research outcome does not only explain massive interaction of protein-protein and protein-nuclear acid by Cascade compound to form molecular machines with efficient immune functions, and it has guiding significant for RNA research field, namely how protein builds unique RNA structure and how RNA involves assembling of protein molecule machine. meanwhile, gene modification technique based on CRISPR has been widely used in gene engineering, and provides a shortcut operation for gene operation in fundamental research in medical science, bioengineering and life science. Therefore, the research outcome is of great reference for further application of CRISPR.

Associate Professor Wei Zhiyi has been actively working in the structure biology, engages in research of interactions mediated by proteins, and has released more than 40 papers. In the past 5 years, he has released more than 10 influential papers at PNAS、Molecular Cell, Science and Cell, in the fields of molecular mechanism of nerve development and assembling mechanism of giant protein mechanism machine with key biological functions.

Paper link: http://www.nature.com/nature/journal/vnfv/ncurrent/full/nature13733.html