Sandbox Reserved 1783: Difference between revisions
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== Structural Overview == | == Structural Overview == | ||
NTCP has 9 transmembrane alpha helices (TM) that form the protein, with an extracellular N-terminus and intracellular C-terminus. NTCP has two domains within the protein, <scene name='95/952711/Panel_domain/ | NTCP has 9 transmembrane alpha helices (TM) that form the protein, with an extracellular N-terminus and intracellular C-terminus. NTCP has two domains within the protein, <scene name='95/952711/Panel_domain/2'>a panel domain</scene>, made up of TM1, TM5, and TM6, and <scene name='95/952711/Core_domain/3'>a core domain</scene>, made up of TM2-4 and TM7-9. An interesting feature of NTCP is the cross of TM3 and TM8 that form an <scene name='95/952711/X_motif/1'>X motif</scene> within the protein that is used in the conformational change of NTCP. The two domains are essential to the conformation change of NTCP to bind bile salts. The intracellular α-helix (ICH) connects TM1 and TM2. The extracellular α-helix connects TM6 and TM7. <Ref name="Xiangbing"> Xiangbing Qi, Wenhui Li. (2022). Unlocking the secrets to human NTCP structure. The Innovation, Vol. 3, Issue 5. 100294, ISSN 2666-6758, [https://doi.org/10.1016/j.xinn.2022.100294 DOI: 10.1016/j.xinn.2022.100294]. </Ref> | ||
There are two significant patches in the NTCP structure that facilitate ligand binding. Residues 84-87 of NTCP are <scene name='95/952711/Binding_patch_1/2'>in Patch 1</scene>, which is located on the TM2-TM3 loop in the core domain. This patch is also considered the extracellular region of the binding tunnel within NTCP. Residues 157-165 of NTCP are associated with <scene name='95/952711/Binding_site_2_with_surface/1'>Patch 2</scene>. They are located on the N-terminal half of the TM5 in the panel domain (residue sequence: KGIVISLVL). Patch 2 is also located in the extracellular region of the binding tunnel. These residues' importance was determined through mutations of these residues and examined through pull-down assays. <ref name="Asami"/> The pre-S1 domain of HBV/HDV binds to the patches on NTCP in order to transport the virus from the exterior of NTCP to the interior binding tunnel to infect human liver cells.<ref name="Goutam"/> | There are two significant patches in the NTCP structure that facilitate ligand binding. Residues 84-87 of NTCP are <scene name='95/952711/Binding_patch_1/2'>in Patch 1</scene>, which is located on the TM2-TM3 loop in the core domain. This patch is also considered the extracellular region of the binding tunnel within NTCP. Residues 157-165 of NTCP are associated with <scene name='95/952711/Binding_site_2_with_surface/1'>Patch 2</scene>. They are located on the N-terminal half of the TM5 in the panel domain (residue sequence: KGIVISLVL). Patch 2 is also located in the extracellular region of the binding tunnel. These residues' importance was determined through mutations of these residues and examined through pull-down assays. <ref name="Asami"/> The pre-S1 domain of HBV/HDV binds to the patches on NTCP in order to transport the virus from the exterior of NTCP to the interior binding tunnel to infect human liver cells.<ref name="Goutam"/> | ||
