The first time in the world! Science at ShanghaiTech University analyzes the first bitter taste receptor structure

On September 16th, the joint research team of Zhijie Liu and Huatian of ShanghaiTech University published a long research paper in the journal Science, which made a major original breakthrough in the structural basis research of strychnine activating the human bitter taste receptor TAS2R46, and unveiled the "mystery" of bitter taste receptor for the first time in the world

Since ancient times, China has said that food is the sky, culinary food culture is an important part of the history of human civilization, and the taste system is an important natural foundation

Type 2 bitter taste receptor (TAS2Rs) is a special class of receptors in the taste system, with low sequence homology with other GPCRs, so it is classified separately as the class T subfamily

Artistic display of different bitter molecules activating the bitter taste receptor TAS2R46 expressed on the taste buds (designed by Julie Liu)

In the past few years, the team and collaborators of Zhijie Liu of Shanghai University of Science and Technology have focused on GPCR research related to major diseases, including systematic research results on cannabinoid receptors (Hua T.

This time, Liu Zhijie and Huatian's research team focused on the bitter taste receptor TAS2R46, which is a broad-spectrum bitter taste perception receptor that can identify a variety of different structural types of bitter molecules, including strychnine, quinine, summer solstice herb, etc

There is a reason why the Class T family of bitter taste receptors as the last unbreached fortress in the GPCR family has encountered unprecedented difficulties in the process of cracking the structure of the bitter taste receptor TAS2R46: the bitter taste receptor is mainly expressed on the surface of taste cells, and the previous GPCR expression technology is not directly applicable

Conformational changes of strychnine structure in both activated and ligand-free states

Through comparative analysis with other activation states of GPCR structures, the research team found that there is a novel activation switch (toggle switch) in TAS2R46 and that the receptor adopts a very unique activation mode

Fig.

This study opens up new avenues for exploring the structure and mechanism of action of bitter taste receptors, fills the gap in the structure of T-class GPCR, and will promote the chemical perception of bitter taste receptors and the exploration
of drug candidate molecules in the future.

The paper is titled "Structural basis for strychnine activation of human bitter taste receptor TAS2R46.
"
。 Weixiu Xu, a 2019 graduate student in the School of Life Science and Technology of ShanghaiTech University, is the first author of the paper; Zhijie Liu, Dean of Avenue College, Executive Director of iHuman Institute, and Professor of the School of Life Sciences and Technology, and Hua Tian, Researcher of iHuman Institute and Assistant Professor of the School of Life Sciences and Technology, are co-corresponding authors
.
ShanghaiTech University was the first to complete
the thesis.

Research Team (Left to Right: Liu Zhijie, Xu Weixiu, Hua Tian)