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The Sixth Forum on Frontiers in Chemical Biology

Source:   Date:2022/10/27

On the morning of October 26, 2022, the State Key Laboratory of Medicinal Chemical Biology held the Sixth Forum on Frontiers in Chemical Biology as scheduled. This forum invited Liu Zhijie, director of the iHuman Institute of Shanghai Tech University, and Ye Sheng, chair professor at Tianjin University to deliver online reports. The forum was hosted by Gong Deshun, a researcher at Nankai University, and featured active participation from Liu Xiangyu, a researcher from Tsinghua University, Professor Yuchi Zhiguang from Tianjin University, Professor Gong Hongri from Nankai University, and Yang Xue, a researcher from Nankai University. The forum was held online through ZOOM and Tencent Meeting platforms and rebroadcast via researchcloud, etc. It has been viewed by 34,000 people.

Professor Liu Zhijie’s report was entitled “The Truths in Receptor Recognition of Human Bitterness & Regulatory Mechanism”. He introduced the important role of G-protein coupled receptors (GPCRs) in signal transduction and their applications in the field of drug screening. The human gustatory sensory system is triggered by the interaction between taste molecules and taste receptors on the tongue and palate. Humans can perceive five tastes: sweet, bitter, salty, sour and fresh. Of these, the perception of sour and salty tastes is mediated by ion channels while the perception of bitter, sweet, and fresh tastes is mediated by GPCRs. Among numerous GPCRs, TAS2Rs are responsible for the bitter taste. With low homology, TAS2Rs and other GPCRs are classified into a separate T-type GPCR subfamily and can recognize different bitter molecules. As TAS2Rs are correlated with many diseases, they are promising targets for pharmacological intervention. However, no experimental structure of a taste receptor has been determined and resolving such structure is key to understanding signal transduction and related drug discovery.

Professor Liu analyzed the cryo-electron microscope structures of the apo TASR46-G protein heterotrimer and its complex with strychnine. Strychnine is a toxic bitter alkaloid, which can activate the signal pathway mediated by TASR46. Through analyzing its structure, Professor Liu explained the role of W88 and E265 amino acids in strychnine binding and determined the characteristics involved in the transition from the apo protein to strychnine binding. He further proposed that Y241 served as a “toggle switch” of receptor activation in receptors.

The report by Professor Ye Sheng was entitled “Cooperative transport mechanism of human monocarboxylate transporter”. Professor Ye introduced the importance of monocarboxylic acid concentration in cells and regulation modes by different cells beginning with the tricarboxylic acid cycle, an important metabolic pathway in humans. The MCT2 protein is crucial for maintaining the monocarboxylic acid concentration in cells and is even related to maintenance of the acidic environment in cancer cells.

From the structure of MCT2 analyzed by cryo-electron microscopy, Professor Ye found the homodimeric state of MCT2 to be significantly different from the heterodimeric form of MCT1. He further explained the specific mechanism by which MCT2 responds to changes in monocarboxylic acid concentration in cells and the mechanistic complexity of its interaction with proton transport coupling, thus providing fresh insights into the action mechanism the of MCT family.

 

During the communication and exchange session, the two professors engaged in in-depth discussions with guests and gave detailed and patient answers to the professional questions from the participating teachers and students.

Liu Zhijie is executive director of the iHuman Institute, ShanghaiTech University, president of the Dadao College of ShanghaiTech University, president of the International Eurasian Academy of Sciences, winner of the First Prize of Shanghai Natural Science Award and a leading talent in Shanghai.

Ye Sheng is a chair professor in Tianjin University, winner of the National Science Fund for Distinguished Young Scholars, a young and middle-aged leading scientific and technological innovator of the 10,000 Talent Initiative, and a New Century Excellent Talent of the Ministry of Education.