Sandbox Reserved 1783: Difference between revisions

The conformational change of NTCP's core domain helices are essential to bile salt binding and uptake. Helices 3 and 8 <scene name='95/952711/X_motif/1'>of the X motif</scene> are the main structural components of the conformational change, as the X motif has highly conserved polar residue motifs that reside near the bile salt transport sites.. The conformational change is energized by the movement of Na+ down its concentration gradient. 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>. Conserved glycine and proline residues act as hinges in the connecting short loops, intracellular α-helices, and extracellular α-helices of NTCP to facilitate the movement of the core and panel domain to allow for a conformational change. The  <scene name='95/952711/Open_pore_ntcp/1'>open</scene> pore is flipped toward the outer membrane to allow for bile salt binding by exposing the Na+ binding sites and the X motif within NTCP. 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. <ref name="Goutam"/>