New progress has been made in the structural mechanism of autophagy receptor protein by Pan Lifeng, Shanghai Institute of organic science, Chinese Academy of Sciences

Autophagy is a highly regulated catabolic process in cells Lysosomes are used to remove protein aggregates, damaged organelles, invading pathogens and other components to cope with internal and external cell pressures and maintain their own dynamic balance Autophagy receptor is a kind of adaptor protein which plays an important role in the process of selective autophagy It can be used as a bridge protein to link the target substrate and autophagy, and thus mediate the selective autophagy process of the target substrate Many human diseases, such as neurodegenerative diseases, are related to the dysfunction or deletion of autophagy receptor protein In recent years, great progress has been made in the research of autophagy receptor protein, but many important deep-seated mechanisms and the pathogenesis of diseases caused by gene mutation have not been well described Pan Lifeng, State Key Laboratory of life organic chemistry, Shanghai Institute of organic chemistry, Chinese Academy of Sciences, has been devoted to the study of the structure and function of autophagy receptor protein for a long time In the previous work of the research group, the structural basis and molecular mechanism of autophagy receptor protein NDP52, tax1bp1 and optineurin recognizing ubiquitin protein were first clarified (autophagy 2015, 10, 1775; autophagy 2018, 14, 66; Journal of molecular biology 2018, 430, 3283), and for the first time revealed the molecular mechanism of autophagy receptor protein optineurin binding to tbk1 kinase and the potential pathogenesis of neurodegenerative diseases caused by mutations of related optineurin and tbk1 genes (nature communications 2016, 7, 12708) Recently, pan Lifeng's research group published a research paper on PNAs entitled "mechanical insights into the interactions of Nap1 with the skichdomains of NDP52 and tax1bp1" (PNAs 2018, 115, e11651) The binding fragments of NDP52 and tax1bp1 interacting with scaffold protein Nap1 were carefully located by means of rapid protein liquid chromatography, isothermal titration calorimetry, analytical ultracentrifugation and nuclear magnetic resonance Then, the ski ch domain binding Nap1 of NDP52 and tax1bp1 was successfully resolved by X-ray crystallography The function of the complex was verified by systematic biochemistry and cell biology experiments The structure of the complex not only elucidates the molecular mechanism of the interaction of autophagy receptor protein NDP52 and tax1bp1 with Nap1, but also reveals a binding mode of the interaction between the ski domain and the action protein for the first time, and explains the tbk1 mediated phosphorylation site in the ski domain of NDP52 and tax1bp1 on the structural level The impact of the role This study fully revealed the molecular mechanism of tbk1 kinase recruitment by autophagy receptor protein NDP52 from a structural perspective, and provided an important structural basis for further understanding the mechanism of autophagy receptor protein NDP52 and tax1bp1 mediated selective autophagy The molecular mechanism of autophagy receptor protein NDP52 and tax1bp1 binding to Nap1 (source: PNAs) Fu Tao, PhD student of Pan Lifeng group, is the first author of this paper The above research work was supported by NSFC, national key R & D project of the Ministry of science and technology, National Youth thousand talents program, strategic leading science and technology project of Chinese Academy of Sciences (class B) and National Key Laboratory of life organic chemistry.