View source for 9qzq


==CryoEM structure of nanodisc-reconstituted human NTCP in complex with grafted NTCP_Nb1 and NabFab==
<StructureSection load='9qzq' size='340' side='right'caption='[[9qzq]], [[Resolution|resolution]] 3.11&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9qzq]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Vicugna_pacos Vicugna pacos]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9QZQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9QZQ 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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene></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=9qzq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9qzq OCA], [https://pdbe.org/9qzq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9qzq RCSB], [https://www.ebi.ac.uk/pdbsum/9qzq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9qzq ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/NTCP_HUMAN NTCP_HUMAN] Familial hypercholanemia. The disease is caused by variants affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/NTCP_HUMAN 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).<ref>PMID:14660639</ref> <ref>PMID:24867799</ref> <ref>PMID:34060352</ref> <ref>PMID:8132774</ref> <ref>PMID:33222321</ref>   (Microbial infection) Acts as a receptor for hepatitis B virus.<ref>PMID:23150796</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Sodium-taurocholate co-transporting polypeptide (NTCP) is a sodium-dependent transporter mediating the hepatic uptake of bile salts and serving as the receptor of hepatitis B and D viruses. While previous studies identified binding sites for sodium ions and substrates, the mechanism remains controversial. We here report a high-resolution structure of NTCP in a closed-tunnel conformation that does not feature substrate binding sites but reveals evidence of two bound sodium ions. To evaluate the functional relevance of this state and gain insight into the transport mechanism, we performed mus-scale molecular dynamics simulations of NTCP starting from distinct conformations and substrate and ion configurations. We observed that both the closed-tunnel and open-tunnel conformations are highly stable, but that the sodium ions and bile salt molecules can shift positions without substantial conformational changes. Our results suggest that the closed-tunnel conformation might represents an inactive state rather than an essential component of a productive transport cycle.

Structure of nanobody-inhibited state of human bile salt transporter NTCP.,Yoon D, Nosol K, Rasouli A, Bang-Sorensen R, Irobalieva RN, Liu H, Tajkhorshid E, Locher KP Structure. 2025 Oct 24:S0969-2126(25)00387-9. doi: 10.1016/j.str.2025.09.012. PMID:41138719<ref>PMID:41138719</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9qzq" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Vicugna pacos]]
[[Category: Bang-Soerensen R]]
[[Category: Irobalieva RN]]
[[Category: Liu H]]
[[Category: Locher KP]]
[[Category: Nosol K]]
[[Category: Rasouli A]]
[[Category: Tajkhorshid E]]
[[Category: Yoon D]]