The Chinese University of Science and Ology analyzes the structure of the human bile salt excret protein electroscope

The national research center of microscale material science of China University of Science and Technology, in collaboration with Professors Chen Yuxing, Zhou Congzhao and Sun Linfeng of the Department of Life Sciences and Medicine, used cryoelectral technology to analyze the near-atomic resolution three-dimensional structure of the human bile salt excrete protein ABCB11, providing a basis for an in-depth understanding of the transport mechanism of this type of membrane protein and the pathogenic mechanism caused by its mutation. The findings were published online in Cell Research.
bile salts are an important part of human bile, synthesized in liver cells by cholesterol as a prelude, and transported by membrane proteins to the bile tube to participate in the formation of bile. Bile mainly helps the digestion and absorption of fatty substances in the small intestine, and blockage of the outer discharge of bile salts can lead to a series of bile silt-related conditions. For example, carried family liver bile siltation (PFIC), benign relapsed liver bile siltation (BRIC), infestational bile siltation (ICP), drug-induced liver damage (DILI). Among them, the most serious bile siltation in the family liver, the disease occurs in children, accompanied by liver swelling, cirrhosis, and even liver failure eventually lead to adult death, most patients with the disease need a liver transplant to survive.
, ABC membrane transport protein ABCB11 on the bile tube is the most important protein in the bile salt excreted into the bile tube. Mutations in the protein-coding gene can lead to the various bile siltation conditions mentioned above. For nearly 20 years since the gene was discovered, reports of research on ABCB11 have continued, but the protein's transport of bile salts remains unclear.
team analyzed the high-resolution three-dimensional structure of the protein's open state by using cryoelectral technology, and analyzed the pathogenicity of the protein's mutants clinically based on the three-dimensional spatial information of the structure. Mutations in clinical samples can disrupt interactions within protein molecules, or misfold proteins, leading to reduced or complete loss of protein transport function, leading to related diseases, the study found. The authors also verified the hydrolysis activity of stimulating adenosine triphosphate from a series of bile salts and two inhibitors (lyphopine, glibenzier), and found that lyphopine and Glibenzene inhibited the activity of the protein in a competitive manner, which is one of the main causes of liver damage caused by taking these drugs. This study not only has important reference significance for the molecular structure of this protein, but also provides theoretical guidance for the analysis of pathogenicity of related diseases and the design of drug development. (Source: Yang Fan, China Science Journal)
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