Hongtao Liu, Dariusz Zakrzewicz, Kamil Nosol, Rossitza N Irobalieva, Somnath Mukherjee, Rose Bang-Sørensen, Nora Goldmann, Sebastian Kunz, Lorenzo Rossi, Anthony A Kossiakoff, Stephan Urban, Dieter Glebe, Joachim Geyer, Kaspar P Locher
Cellular entry of the hepatitis B and D viruses (HBV/HDV) requires binding of the viral surface polypeptide preS1 to the hepatobiliary transporter Na+ -taurocholate co-transporting polypeptide (NTCP). This interaction can be blocked by bulevirtide (BLV, formerly Myrcludex B), a preS1 derivative and approved drug for treating HDV infection. Here, to elucidate the basis of this inhibitory function, we determined a cryo-EM structure of BLV-bound human NTCP. BLV forms two domains, a plug lodged in the bile salt transport tunnel of NTCP and a string that covers the receptor's extracellular surface...
March 20, 2024: Nature Communications