Sandbox Reserved 1783: Difference between revisions

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There are two significant areas in the NTCP structure that facilitate ligand binding, which are referred to as "patches." Residues 84-87 of NTCP are patch 1, which are located on the TM2-TM3 loop in the core domain. This is also considered the extracellular region of NTCP “tunnel." Residues 157-165 NTCP are associated with patch 2. They are located on N-terminal half of the TM5 in the panel domain (residue sequence: KGIVISLVL). Patch 2 is also located in th extracellular region. These residues' importance was determined through mutations of these residues and examined through pull-down assays <ref name="Asami"/>.
There are two significant areas in the NTCP structure that facilitate ligand binding, which are referred to as "patches." Residues 84-87 of NTCP are patch 1, which are located on the TM2-TM3 loop in the core domain. This is also considered the extracellular region of NTCP “tunnel." Residues 157-165 NTCP are associated with patch 2. They are located on N-terminal half of the TM5 in the panel domain (residue sequence: KGIVISLVL). Patch 2 is also located in th extracellular region. These residues' importance was determined through mutations of these residues and examined through pull-down assays <ref name="Asami"/>.
[[Image:Figuredomain.png|450 px|right|thumb|'''Figure 3.''' Cartoon of NTCP topology.]]


=== Binding Pocket ===
=== Binding Pocket ===
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=== Conformation Change ===
=== Conformation Change ===
[[Image:Figuredomain.png|450 px|right|thumb|'''Figure 3.''' Cartoon of NTCP topology.]]


The conformational change of NTCP's core domain helices are essential to bile salt binding and uptake. Figure 1 displays the topology of NTCP, highlighting both the panel (shown in blue) and core (shown in purple and pink) domains  <ref name="Xiangbing"/>. Helices 3 and 8 are the main structural components of the conformational change. Before bile salt can bind, the pore in which salt binds must be <scene name='95/952711/Open_pore_ntcp_non_transparent/1'>open</scene>. The <scene name='95/952711/Open_pore_ntcp/1'>open</scene> pore is flipped toward the outer membrane to allow for binding. Once <scene name='95/952711/Open_pore_with_bile_salts/1'>bound</scene>, the pore is <scene name='95/952711/Closed_pore_ntcp/1'>closed</scene>, and bile salt is able to be released into the cell, past the inner membrane.
The conformational change of NTCP's core domain helices are essential to bile salt binding and uptake. Figure 1 displays the topology of NTCP, highlighting both the panel (shown in blue) and core (shown in purple and pink) domains  <ref name="Xiangbing"/>. Helices 3 and 8 are the main structural components of the conformational change. Before bile salt can bind, the pore in which salt binds must be <scene name='95/952711/Open_pore_ntcp_non_transparent/1'>open</scene>. The <scene name='95/952711/Open_pore_ntcp/1'>open</scene> pore is flipped toward the outer membrane to allow for binding. Once <scene name='95/952711/Open_pore_with_bile_salts/1'>bound</scene>, the pore is <scene name='95/952711/Closed_pore_ntcp/1'>closed</scene>, and bile salt is able to be released into the cell, past the inner membrane.
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