8HRY

Cryo-EM structure of human NTCP-myr-preS1-YN9016Fab complex

Summary for 8HRY

• Entry DOI: 10.2210/pdb8hry/pdb
• EMDB information: 34982
• Descriptor: Sodium/bile acid cotransporter, Large S protein (Fragment), Fab heavy chain from antibody IgG clone number YN9016, ... (4 entities in total)
• Functional Keywords: hepatitis, hbv, transport protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 93402.07

Authors

Asami, J.,Shimizu, T.,Ohto, U. (deposition date: 2022-12-16, release date: 2024-01-17, Last modification date: 2024-11-06)

Primary citation

Asami, J.,Park, J.H.,Nomura, Y.,Kobayashi, C.,Mifune, J.,Ishimoto, N.,Uemura, T.,Liu, K.,Sato, Y.,Zhang, Z.,Muramatsu, M.,Wakita, T.,Drew, D.,Iwata, S.,Shimizu, T.,Watashi, K.,Park, S.Y.,Nomura, N.,Ohto, U.
Structural basis of hepatitis B virus receptor binding.
Nat.Struct.Mol.Biol., 31:447-454, 2024

PubMed Abstract: Hepatitis B virus (HBV), a leading cause of developing hepatocellular carcinoma affecting more than 290 million people worldwide, is an enveloped DNA virus specifically infecting hepatocytes. Myristoylated preS1 domain of the HBV large surface protein binds to the host receptor sodium-taurocholate cotransporting polypeptide (NTCP), a hepatocellular bile acid transporter, to initiate viral entry. Here, we report the cryogenic-electron microscopy structure of the myristoylated preS1 (residues 2-48) peptide bound to human NTCP. The unexpectedly folded N-terminal half of the peptide embeds deeply into the outward-facing tunnel of NTCP, whereas the C-terminal half formed extensive contacts on the extracellular surface. Our findings reveal an unprecedented induced-fit mechanism for establishing high-affinity virus-host attachment and provide a blueprint for the rational design of anti-HBV drugs targeting virus entry.

PubMed: 38233573
DOI: 10.1038/s41594-023-01191-5

Experimental method

ELECTRON MICROSCOPY (3.11 Å)