Sandbox Reserved 1782

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*The NTCP binding pocket represents a "tunnel" lined with hydrophilic residues within the NTCP structure to allow hydrophilic bile salts and sodium ions to bind. When there are no bile salts bound to NTCP's binding tunnel, it forms a hollow hole in the middle of the structure, from <scene name='95/952710/Tunnel_front/1'>front</scene> to <scene name='95/952710/Tunnel_front/3'>back</scene>. As bile salts bind to this binding pocket, the bile salts very nicely fill the hole within NTCP and fit almost perfectly within the tunnel, to the point where the <scene name='95/952710/Bile_bound_to_tunnel/2'>tunnel</scene> can no longer be seen, as it is completely encompassing the bile salts. This tunnel formed connects the external cytoplasm of the hepatocyte to the inner leaflet of the basolateral membrane. The side of the tunnel where the bile salts bind are lined with hydrophilic residues, whereas the opposite side of the helix is lined with hydrophobic residues, as the transmembrane helices are amphipathic. <Ref name="Liu"> Liu, H., Irobalieva, R.N., Bang-Sørensen, R. et al. Structure of human NTCP reveals the basis of recognition and sodium-driven transport of bile salts into the liver. Cell Res 32, 773–776 (2022). [https://doi.org/10.1038/s41422-022-00680-4 DOI: 10.1038/s41422-022-00680-4]. </Ref>.
*The NTCP binding pocket represents a "tunnel" lined with hydrophilic residues within the NTCP structure to allow hydrophilic bile salts and sodium ions to bind. When there are no bile salts bound to NTCP's binding tunnel, it forms a hollow hole in the middle of the structure, from <scene name='95/952710/Tunnel_front/1'>front</scene> to <scene name='95/952710/Tunnel_front/3'>back</scene>. As bile salts bind to this binding pocket, the bile salts very nicely fill the hole within NTCP and fit almost perfectly within the tunnel, to the point where the <scene name='95/952710/Bile_bound_to_tunnel/2'>tunnel</scene> can no longer be seen, as it is completely encompassing the bile salts. This tunnel formed connects the external cytoplasm of the hepatocyte to the inner leaflet of the basolateral membrane. The side of the tunnel where the bile salts bind are lined with hydrophilic residues, whereas the opposite side of the helix is lined with hydrophobic residues, as the transmembrane helices are amphipathic. <Ref name="Liu"> Liu, H., Irobalieva, R.N., Bang-Sørensen, R. et al. Structure of human NTCP reveals the basis of recognition and sodium-driven transport of bile salts into the liver. Cell Res 32, 773–776 (2022). [https://doi.org/10.1038/s41422-022-00680-4 DOI: 10.1038/s41422-022-00680-4]. </Ref>.
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*[[Image:Patches.png|400 px|left|thumb|'''Figure 1.''' Surface representation of the NTCP molecule with both patches shown. Patch 1 can be seen on the left side of the molecule, whereas patch 2 is located on the right side within the binding tunnel. PDB file 7ZYI.]]The binding pocket of NTCP contains two patches on its exterior. These two patches are used for assisting in the binding of bile salts into the binding tunnel. These external patches are extremely important for aiding in the transport of bile salts from the exterior of NTCP to the interior binding tunnel <ref name="Asami"/>. Patch 1 is made up of residues 84-87 of NTCP and Patch 2 consists of residues 157-165. Patch 1 is located on the poles of NTCP, namely the top of the structure, within the TM2-TM3 transmembrane loop, whereas patch 2 is located towards the middle of the NTCP molecule within transmembrane 5 (TM5). These two patches are also predominantly responsible for binding the preS1 binding region of the HBV/HDV virus. Patch 2 also forms a part of the binding tunnel previously mentioned <ref name="Asami"/>.
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[[Image:Patches.png|400 px|left|thumb|'''Figure 1.''' Surface representation of the NTCP molecule with both patches shown. Patch 1 can be seen on the left side of the molecule, whereas patch 2 is located on the right side within the binding tunnel. PDB file 7ZYI.]]
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*The binding pocket of NTCP contains two patches on its exterior. These two patches are used for assisting in the binding of bile salts into the binding tunnel. These external patches are extremely important for aiding in the transport of bile salts from the exterior of NTCP to the interior binding tunnel <ref name="Asami"/>. Patch 1 is made up of residues 84-87 of NTCP and Patch 2 consists of residues 157-165. Patch 1 is located on the poles of NTCP, namely the top of the structure, within the TM2-TM3 transmembrane loop, whereas patch 2 is located towards the middle of the NTCP molecule within transmembrane 5 (TM5). These two patches are also predominantly responsible for binding the preS1 binding region of the HBV/HDV virus. Patch 2 also forms a part of the binding tunnel previously mentioned <ref name="Asami"/>.
== Mechanism ==
== Mechanism ==

Revision as of 19:08, 27 March 2023

This Sandbox is Reserved from February 27 through August 31, 2023 for use in the course CH462 Biochemistry II taught by R. Jeremy Johnson at the Butler University, Indianapolis, USA. This reservation includes Sandbox Reserved 1765 through Sandbox Reserved 1795.
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human Sodium Taurocholate Co-transporting Polypeptide (NTCP) structure

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References

  1. ↑ Goutam, K., Ielasi, F.S., Pardon, E. et al. Structural basis of sodium-dependent bile salt uptake into the liver. Nature 606, 1015–1020 (2022). DOI: 10.1038/s41586-022-04723-z.
  2. ↑ Maldonado-Valderrama, J., Wilde, P., Macierzanka, A., & Mackie, A. (2011). The role of bile salts in digestion. Advances in colloid and interface science, 165(1), 36–46. DOI: 10.1016/j.cis.2010.12.002.
  3. ↑ 3.0 3.1 3.2 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. Structure of the bile acid transporter and HBV receptor NTCP. Nature. 2022 Jun; 606 (7916):1021-1026. DOI: 10.1038/s41586-022-04845-4.
  4. ↑ Liu, H., Irobalieva, R.N., Bang-Sørensen, R. et al. Structure of human NTCP reveals the basis of recognition and sodium-driven transport of bile salts into the liver. Cell Res 32, 773–776 (2022). DOI: 10.1038/s41422-022-00680-4.

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