Lei Xiaoguang and Wang Chu discover the Chemoproteomic Profiling of Bile Acid Interacting Proteins

MAY . 25 2017

Peking University, May 16, 2017: Recently, a research article titled Chemoproteomic Profiling of Bile Acid Interacting Proteins, led by Prof. Lei Xiaoguang and Prof. Wang Chu of the College of Chemistry and Molecular Engineering, PKU, was published by ACS Central Science. According to the article, over 600 bile acid interacting proteins, including a number of novel targets have been identified through a chemoproteomic approach, the findings will significantly enhance the current understanding of bile acid regulatory roles in human physiology and disease.

Bile acids are a class of important endogenous metabolites synthesized from cholesterol in the liver and modified by microbiota in gut. Being amphipathic molecules, the major function of bile acids is to assist in dietary lipid digestion. In addition, they also act as signaling molecules to regulate lipids and glucose metabolism, as well as gut microbiota composition in the host. Disorders in bile acid metabolism are closely related to metabolic syndromes and intestinal and neurodegenerative diseases. Though bile acid based therapies have been clinically implemented for decades, the regulatory mechanism of bile acids is still poorly understood and a comprehensive characterization of bile acid interacting proteins in proteomes remains elusive.

Current approaches to study bile acid protein interactions mainly rely on traditional molecular biotechnologies and genetic mouse models. While they can discover a number of individual bile acid protein interactions in a case-by-case manner, the low throughput puts great limitation on gaining a deeper and broader understanding of bile acid mechanisms of action.

Inspired by the previous efforts to map cholesterol-binding and lipid-binding proteins in proteomes using activity-based protein profiling, the team led by Prof. Lei Xiaoguang and Prof. Wang Chu describes a chemoproteomic strategy that uses a number of structurally diverse, clickable, and photoreactive bile acid based probes in combination with quantitative mass spectrometry to globally profile bile acid interacting proteins in mammalian cells.

Gel-based profiling of bile acid interacting proteins in living cells

Over 600 bile acid interacting protein targets were identified, including known endogenous receptors and transporters of bile acid. Analysis of these novel bile acid interacting proteins reveals that they are mainly enriched in functional pathways such as endoplasmic reticulum stress response and lipid metabolism, and are predicted with strong implications with Alzheimer’s disease, non-alcoholic fatty liver disease and diarrhea. The study provides the first global map of bile acid interacting proteins in mammalian cells that will serve as a valuable resource for exploring and understanding bile acid biology.

Bile acid biology

Bioinformatic analysis of bile acid interacting proteins

Zhuang Shentian, Ph.D, and Li Qiang, Ph.D, are co-first authors on the research article and Prof. Lei Xiaoguang and Prof. Wang Chu are corresponding authors. The research project was co-funded by National Natural Science Foundation Committee, Ministry of Science and Technology of China and Peking-Tsinghua Center for Life Sciences. 
Background information:
ACS Central Science: A multidisciplinary journal that publishes the most compelling, important primary reports on research in chemistry and in allied fields, wherein chemical approaches play a key role. It is also the first fully open access journal published by the American Chemical Society.
Written by: Li Xiaotong
Edited by: Wang Yuqing/ Gan Zhonghao
Source: PKU News (Chinese)