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The 3D structure of the liver ‘Entrance Gate’ can trigger treatments to fight hepatitis

Although it is an essential gateway to the liver, NTCP has not been clearly described before. Na+-taurocholate co-transport polypeptide (NTCP) is a protein located exclusively in the liver cell membrane that allows the recycling of bile acid molecules. It is also the cellular receptor of human hepatitis B and D viruses (HBV/HDV). A better understanding of NTCP can allow the development of treatments specifically designed for the liver, and combat HBV and HDV infection.

The 3D structure of the liver ‘Entrance Gate’ can trigger treatments to fight hepatitis
The 3D structure of the liver ‘Entrance Gate’ can trigger treatments to fight hepatitis

NTCP is a protein that is difficult to study. It weighs only 38 kilodaltons (kDa),[1], while cold electron microscopy, the technology used to study this type of molecule, only works for molecules weighing more than 50 kDA. Therefore, the challenge is to “expand” and stabilize it.

To do this, teams from French and Belgian laboratories[2] developed and tested a collection of antibody fragments targeting NTCP. The 3D structures of the resulting complexes are determined using cold electron microscopes, and different segments of antibodies are stabilized and reveal some form of NTCP.

The team of scientists was able to describe two necessary NTCP structures: one in which the protein opens a large membrane hole to contain bile salts, which HBV and HDV can bind, and the second, ‘closed’, which prevents the recognition of the virus. .

The first structure, “open” is very surprising, since no other known molecular transporter forms such an “enlarged” pore. In turn, the second structure could help find antiviral molecules that prevent HBV and HDV infection. The team of researchers intends to continue their work to fully clarify the functionality of the NTCP.

Reference: “The structural basis of the absorption of sodium-dependent bile salts on the liver” by Kapil Goutam, Francesco S. Ielasi, Els Pardon, Jan Steyaert and Nicolas Reyes, May 11, 2022, Nature.
DOI: 10.1038 / s41586-022-04723-z

Notes

A kilodalton is a unit of atomic mass equal to 1,000 daltons. A dalton is one-twelfth the mass of a carbon-12 atom (approximately the mass of a hydrogen atom).
The study was carried out by teams at the MPF Laboratory (Microbiologie fondamentale et… This study was supported by the ANRS Emerging Infectious Diseases Program, along with other programs.

Written by hoangphat

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