View source for 7vaf


==Cryo-EM structure of Rat NTCP complexed with YN69202Fab==
<StructureSection load='7vaf' size='340' side='right'caption='[[7vaf]], [[Resolution|resolution]] 3.11&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7vaf]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7VAF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7VAF FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.11&#8491;</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7vaf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7vaf OCA], [https://pdbe.org/7vaf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7vaf RCSB], [https://www.ebi.ac.uk/pdbsum/7vaf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7vaf ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/NTCP_RAT NTCP_RAT] 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:1961729). It is strictly dependent on the extracellular presence of sodium (PubMed:1961729). 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:9486191). 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 (By similarity).[UniProtKB:Q14973]<ref>PMID:1961729</ref> <ref>PMID:9486191</ref> 
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== Publication Abstract from PubMed ==
Chronic infection with hepatitis B virus (HBV) affects more than 290 million people worldwide, is a major cause of cirrhosis and hepatocellular carcinoma, and results in an estimated 820,000 deaths annually(1,2). For HBV infection to be established, a molecular interaction is required between the large glycoproteins of the virus envelope (known as LHBs) and the host entry receptor sodium taurocholate co-transporting polypeptide (NTCP), a sodium-dependent bile acid transporter from the blood to hepatocytes(3). However, the molecular basis for the virus-transporter interaction is poorly understood. Here we report the cryo-electron microscopy structures of human, bovine and rat NTCPs in the apo state, which reveal the presence of a tunnel across the membrane and a possible transport route for the substrate. Moreover, the cryo-electron microscopy structure of human NTCP in the presence of the myristoylated preS1 domain of LHBs, together with mutation and transport assays, suggest a binding mode in which preS1 and the substrate compete for the extracellular opening of the tunnel in NTCP. Our preS1 domain interaction analysis enables a mechanistic interpretation of naturally occurring HBV-insusceptible mutations in human NTCP. Together, our findings provide a structural framework for HBV recognition and a mechanistic understanding of sodium-dependent bile acid translocation by mammalian NTCPs.

Structure of the bile acid transporter and HBV receptor NTCP.,Asami J, Kimura KT, Fujita-Fujiharu Y, Ishida H, Zhang Z, Nomura Y, Liu K, Uemura T, Sato Y, Ono M, Yamamoto M, Noda T, Shigematsu H, Drew D, Iwata S, Shimizu T, Nomura N, Ohto U Nature. 2022 Jun;606(7916):1021-1026. doi: 10.1038/s41586-022-04845-4. Epub 2022 , May 17. PMID:35580629<ref>PMID:35580629</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
*[[Antibody 3D structures|Antibody 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Rattus norvegicus]]
[[Category: Asami J]]
[[Category: Ohto U]]
[[Category: Shimizu T]]