discovery of the 3D structure of the gate to the liver

– Researchers have just characterized a crucial protein in liver cells, which is difficult to study.
– Its structure has been described for the first time and one of the forms it uses prevents infection of certain virus (A virus is a biological entity that requires a host cell that it uses …) of’hepatitis (Hepatitis (from Greek hepar: liver) means any acute inflammation or …).
– These results can guide research (Scientific research initially identifies all the measures taken with a view to …) therapeutic tools against hepatitis virus infection.


Illustration of the two 3D conformations that the NTCP can adopt. On the left, the “open” form that HBV and HDV can bind to, and on the right the “closed” form, which prevents targeting of viruses. © Kapil Goutam / Nicolas Reyes / CNRS

Researchers from CNRS (The National Center for Scientific Research, better known by its acronym CNRS, is the largest …)of’The Pastoral Institute (Institut Pasteur is a private non-profit French fund, which …)of’Institute (An institute is a permanent organization created for a specific purpose. It is …) Flemish of biotechnology (OECD defines biotechnology as “the application of the principles …) and ofThe Free University of Brussels (The Free University of Brussels (ULB) is a French-speaking Belgian university.) has just provided the first study of the structure and function of one protein (A protein is a biological macromolecule composed of one or more …) central liver (The liver is a strange and asymmetrical abdominal organ that houses in humans in …): NTCP, gateway for bile salts, but also for certain hepatitis viruses. Published in the journal Nature, these results reveal the 3D structure of NTCP and two forms it can take. One of them could help with the development point (graphics) therapeutic tools against hepatitis virus infection.

It is an important gateway to the liver, but still little described to this day. NTCP (to Na + taurocholate co-transporting polypeptide) is a protein located in the membrane of liver cells and exclusive to these cells, allowing them to reuse bile acids. It is also the target of human virusesHepatitis B (Hepatitis B is viral hepatitis due to infection with the virus of …) and D (HBV / HDV). A better understanding of it could therefore, on the one hand, lead to the development of treatments specifically targeted to the liver, and on the other hand to combat HBV and HDV infection.

NTCP is a difficult protein to study. It weighs only 38 kilodaltons (kDa) while it technology (The word technology has two de facto meanings 🙂 used to study this type of molecule, cryo-electron microscopy only works for molecules if weight (Weight is the force of gravity, of gravitational and inertial origin, exercised by …) is greater than 50 kDA. All (The whole understood as the whole of what exists is often interpreted as the world or …) the challenge was therefore to “increase” and stabilize it.

For this, teams from French and Belgian laboratories have developed and tested a whole collection of antibody fragments directed against NTCP. The 3D structure of the complexes thus formed was able to be determined by electron cryo-microscopy and then traced back to the protein. The different antibody fragments have also made it possible to stabilize several forms of NTCP and thus observe them.

The research team was able to describe two conformations that NTCP can adopt: a first, where the protein opens a wide entrance portal for bile salts, to which HBV and HDV can bind, and a second, “closed”, folded in such a way that it prevents virus targeting.

The first confirmation (In chemistry, the conformation of a molecule is the spatial arrangement of the atoms that make it up …)“open” is very surprising because no one else transporter (A carrier runs a commercial company specializing in the transport of …) molecule known form of pore of this kind, “wide open”. The other could help in looking for the search for molecules that prevent HBV and HDV infection. The research team now intends to continue its work to fully shed light on the function of the NTCP.

Bibliography:
Structural basis for sodium dependent galde (Bile is a greenish-yellow, alkaline liquid (pH between 7.6 and 8.6) that promotes …) salt uptake into the liver.
Kapil Goutam, Francesco S. Ielasi, Els Pardon, Jan Steyaert and Nicolas Reyes.
NatureMay 11, 2022. DOI: 10.1038 / s41586-022-04723-z.

contacts:
-Nicolas Reyes- Searching (A researcher (fifth researcher) refers to a person whose task is to research …) CNRS – n.reyes at iecb.u-bordeaux.fr
– François Maginiot – CNRS press manager – francois.maginiot at cnrs.fr

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