8rqf

Cryo-EM structure of human NTCP-Bulevirtide complex

spinqualitylabelsall models 8rqf, resolution 3.41Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8rqf is a 5 chain structure with sequence from Homo sapiens, Lama glama and Hepatitis B virus genotype C. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.41Å Ligands: BJU Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed 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. The N-terminally attached myristoyl group of BLV interacts with the lipid-exposed surface of NTCP. Our structure reveals how BLV inhibits bile salt transport, rationalizes NTCP mutations that decrease the risk of HBV/HDV infection, and provides a basis for understanding the host specificity of HBV/HDV. Our results provide opportunities for structure-guided development of inhibitors that target HBV/HDV docking to NTCP. Structure of antiviral drug bulevirtide bound to hepatitis B and D virus receptor protein NTCP.,Liu H, Zakrzewicz D, Nosol K, Irobalieva RN, Mukherjee S, Bang-Sorensen R, Goldmann N, Kunz S, Rossi L, Kossiakoff AA, Urban S, Glebe D, Geyer J, Locher KP Nat Commun. 2024 Mar 20;15(1):2476. doi: 10.1038/s41467-024-46706-w. PMID:38509088 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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