8hry | pdb_00008hry

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

spinqualitylabelsall models 8hry, resolution 3.11Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8hry is a 4 chain structure with sequence from Hepatitis B virus, Homo sapiens and Ondatra zibethicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.11Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease NTCP_HUMAN Familial hypercholanemia. The disease is caused by variants affecting the gene represented in this entry. Function NTCP_HUMAN As a major transporter of conjugated bile salts from plasma into the hepatocyte, it plays a key role in the enterohepatic circulation of bile salts necessary for the solubilization and absorption of dietary fat and fat-soluble vitamins (PubMed:14660639, PubMed:24867799, PubMed:34060352, PubMed:8132774). It is strictly dependent on the extracellular presence of sodium (PubMed:14660639, PubMed:24867799, PubMed:34060352, PubMed:8132774). It exhibits broad substrate specificity and transports various bile acids, such as taurocholate, cholate, as well as non-bile acid organic compounds, such as estrone sulfate (PubMed:14660639, PubMed:34060352). Works collaboratively with the ileal transporter (NTCP2), the organic solute transporter (OST), and the bile salt export pump (BSEP), to ensure efficacious biological recycling of bile acids during enterohepatic circulation (PubMed:33222321). (Microbial infection) Acts as a receptor for hepatitis B virus. Publication Abstract from PubMed 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. Structural basis of hepatitis B virus receptor binding.,Asami J, Park JH, 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 SY, Nomura N, Ohto U Nat Struct Mol Biol. 2024 Mar;31(3):447-454. doi: 10.1038/s41594-023-01191-5. , Epub 2024 Jan 17. PMID:38233573 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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