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Under the microscope: NTCP

This month: NTCP

What is NTCP?

Sodium (Na) taurocholate cotransporting polypeptide (NTCP) is a protein located exclusively in the membrane of liver cells that enables recycling of bile acid molecules. It is also the cellular receptor of human hepatitis B and D viruses (HBV/HDV).

Why are we looking at it?

A better understanding of NTCP could enable the development of treatments specifically designed for the liver, and to fight HBV and HDV infection. I’m assuming there’s some research into this. Spot on. Teams from French and Belgian laboratories have been working together on NTCP, but it is a difficult protein to study.

What’s the issue?

It weighs only 38 kilodaltons (kDa), whereas cryo-electron microscopy (the technology used to study this type of molecule) only works for molecules weighing more than 50 kDa. The challenge was, therefore, to “enlarge” and stabilise it.

So what did they do?

The teams developed and tested a collection of antibody fragments targeting NTCP.  The 3D structures of the resulting complexes were determined using cryo-electron microscopy, and different antibody fragments stabilised and revealed several forms of NTCP.

What did they find?

They have described two essential NTCP conformations: one in which the protein opens a large membrane pore to bile salts, to which HBV and HDV can bind, and a second, “closed” conformation, that prevents recognition by the viruses.

Where can I read more?

They have published a paper in Nature, which can be read here

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