Sandbox Reserved 1794: Difference between revisions
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In order to reveal these binding sites to initiate bile salt transport, NTCP exists in two different conformations; the <scene name='95/952722/Open_pore_conf/4'>open pore conformation</scene> and the <scene name='95/952722/Inward_facing_conf/1'>inward facing conformation</scene>. <ref name="Goutam"/> NTCP undergoes a conformational change from inward facing to open pore which exposes the binding sites to the extracellular region to allow the sodium ions and bile salts to bind. NTCP utilizes an [https://www.sciencedirect.com/science/article/pii/S0092867417302891 elevator-alternating mechanism] <Ref name = "Latorraca"> Latorraca, N. R.; Fastman, N. M.; Venkatakrishnan, A. J.; Frommer, W. B.; Dror, R. O.; Feng, L. Mechanism of Substrate Translocation in an Alternating Access Transporter. Cell 2017, 169 (1), 96–107. </ref> where one domain <font color=' | In order to reveal these binding sites to initiate bile salt transport, NTCP exists in two different conformations; the <scene name='95/952722/Open_pore_conf/4'>open pore conformation</scene> and the <scene name='95/952722/Inward_facing_conf/1'>inward facing conformation</scene>. <ref name="Goutam"/> NTCP undergoes a conformational change from inward facing to open pore which exposes the binding sites to the extracellular region to allow the sodium ions and bile salts to bind. NTCP utilizes an [https://www.sciencedirect.com/science/article/pii/S0092867417302891 elevator-alternating mechanism] <Ref name = "Latorraca"> Latorraca, N. R.; Fastman, N. M.; Venkatakrishnan, A. J.; Frommer, W. B.; Dror, R. O.; Feng, L. Mechanism of Substrate Translocation in an Alternating Access Transporter. Cell 2017, 169 (1), 96–107. </ref> where one domain <font color='red'><b>(panel)</b></font> does most of the translocation, and the other domain <font color='#6060ff'><b>(core)</b></font> remains stationary. <Ref name = "Asami"> Asami, J., Kimura, K.T., Fujita-Fujiharu, Y. et al.Structure of the bile acid transporter and HBV receptor NTCP. Nature 606, 1021–1026 (2022). https://doi.org/10.1038/s41586-022-04845-4 </ref> In this movement, the <scene name='95/952722/Ntcp_core_domain-_blue/8'>core domain</scene> and the <scene name='95/952722/Ntcp_panel_domain-_red/4'>panel domain</scene> rotate 20° with the <font color='red'><b>panel domain</b></font> moving 5 Å away from the <font color='#6060ff'><b>core domain</b></font>, which remains relatively rigid. This conformational change reveals the two sodium ion binding sites as well as the <scene name='95/952721/Amphipathic_patterns/2'>amphipathic pore</scene> in the membrane. The movement of the panel domain is facilitated by <scene name='95/952722/Pro_and_gly_hinges/5'>proline and glycine residues</scene> located in the <scene name='95/952722/Connector_helices/6'>connector helices</scene> between the panel and core domains. <scene name='95/952722/Pro_and_gly_hinges/7'>These residues</scene> <font color='#FCE205'><b>(yellow)</b></font> act as hinges that assist in the movement of the panel domain away from the core domain. <ref name="Goutam"/> | ||
== Bile Salt Transport == | == Bile Salt Transport == | ||
