– Its structure has been described for the first time, and one of the forms it adopts prevents infection by certain virus (A virus is a biological entity that requires a host cell, which it uses…) of the’hepatitis (Hepatitis (from the Greek hepar: liver) means any acute inflammation or…).
– These results could guide the research (Scientific research designates in the first place all the actions undertaken with a view to…) therapeutic tools against hepatitis virus infection.
Illustration of the two 3D conformations that NTCP can adopt. On the left, the “open” form to which HBV and HDV can bind and on the right the “closed” form which prevents targeting by viruses.© Kapil Goutam/Nicolas Reyes/CNRS
Scientists from CNRS (The National Center for Scientific Research, better known by its acronym CNRS, is the largest…)of the’Pastor Institute (The Institut Pasteur is a private non-profit French foundation which…)of the’Institute (An institute is a permanent organization created for a certain purpose. It is…) flemish of biotechnology (The OECD defines biotechnology as « the application of the principles…) and of theFree University of Brussels (The Free University of Brussels (ULB) is a French-speaking Belgian university.) have just delivered the first study of the structure and functioning of a protein (A protein is a biological macromolecule composed of one or more…) central liver (The liver is an odd and asymmetrical abdominal organ, housed 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 essential gateway to the liver, yet still little described until today. NTCP (for Na+-taurocholate co-transporting polypeptide) is a protein located in the membrane of liver cells, and exclusive to these cells, which allows them to recycle bile acids. It is also the target of human viruses of theHepatitis B (Hepatitis B is viral hepatitis due to infection with the virus of…) and D (HBV/HDV). A better understanding of it could therefore lead on the one hand to the development of treatments specifically targeting the liver, and on the other hand to fight against HBV and HDV infection.
NTCP is a difficult protein to study. It weighs only 38 kilodaltons (kDa) while the technology (The word technology has two de facto meanings:) used to study this type of molecule, cryo-electron microscopy only works for molecules whose weight (Weight is the force of gravity, of gravitational and inertial origin, exerted by the…) 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 targeting NTCP. The 3D structure of the complexes thus formed was able to be determined by electron cryo-microscopy and then traced back to that of the protein. The different antibody fragments have also made it possible to stabilize several forms of NTCP and thus to observe them.
The research team was able to describe two conformations that NTCP can adopt: a first where the protein opens a wide portal of entry for bile salts, to which HBV and HDV can attach, and a second, « closed » , folded in such a way that it prevents targeting by viruses.
The first one conformation (In chemistry, the conformation of a molecule is the spatial arrangement of the atoms that compose it….)« open », is very surprising, because no other carrier (A carrier runs a commercial business specializing in the transportation of…) molecule known form of pore of this kind, « wide open ». The second could help guide the search for molecules that prevent HBV and HDV infection. The research team now intends to continue its work to fully elucidate the functioning of NTCP.
Bibliography:
Structural basis of sodium-dependent bile (Bile is a greenish-yellow, basic fluid (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- Searcher (A researcher (fem. researcher) refers to a person whose job is to do research…) CNRS – n.reyes at iecb.u-bordeaux.fr
– François Maginiot – CNRS press officer – francois.maginiot at cnrs.fr
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