Sandbox Reserved 1619: Difference between revisions
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== Structural highlights == | == Structural highlights == | ||
===Substrate Structure=== | ===Substrate Structure=== | ||
[[Image:App.png|250 px|right|thumb|'''Figure 1. APP fragment conformational change in gamma secretase.''' APP bound to | [[Image:App.png|250 px|right|thumb|'''Figure 1. APP fragment conformational change in gamma secretase.''' APP bound to GS undergoes a conformational change. The free state consists of 2 helices. Once bound to GS, the N-terminal helix unfolds into a coil and the C-terminal helix unwinds into a β-strand. This β-strand interacts with PS1 and is the site of cleavage by the protease.]] | ||
GS has been structurally characterized in the presence of both [https://en.wikipedia.org/wiki/Amyloid_precursor_protein/ APP] and Notch substrates. In each of these structures, the substrate bound in a similar location and underwent a similar structural transition upon binding to the active site of GS. Each substrate is composed of an N-terminal loop and a transmembrane helix. The peptide substrate enters the enzyme by <scene name='83/832945/App_in_gs_general/1'>lateral diffusion</scene> via the lid complex, and once in place, the TM helix of the substrate is anchored by <scene name='83/832945/Hydrophobic_interactions/2'>van der Waals contacts</scene>. Upon binding to GS, the C-terminal extracellular helix of the substrate unwinds. The substrate's N-terminal end of the TM helix unwinds into a β-strand (Fig. 1). To differentiate substrates, the β-strand is often the main point of identification for the enzyme. Substrate binding induces a structural change in GS, creating two β-strands that form a β-sheet with the one β-strand of the substrate. This β-sheet is in close proximity with the active site, and guides the process of catalysis.<ref name="Zhou">PMID:30630874</ref> | GS has been structurally characterized in the presence of both [https://en.wikipedia.org/wiki/Amyloid_precursor_protein/ APP] and Notch substrates. In each of these structures, the substrate bound in a similar location and underwent a similar structural transition upon binding to the active site of GS. Each substrate is composed of an N-terminal loop and a transmembrane helix. The peptide substrate enters the enzyme by <scene name='83/832945/App_in_gs_general/1'>lateral diffusion</scene> via the lid complex, and once in place, the TM helix of the substrate is anchored by <scene name='83/832945/Hydrophobic_interactions/2'>van der Waals contacts</scene>. Upon binding to GS, the C-terminal extracellular helix of the substrate unwinds. The substrate's N-terminal end of the TM helix unwinds into a β-strand (Fig. 1). To differentiate substrates, the β-strand is often the main point of identification for the enzyme. Substrate binding induces a structural change in GS, creating two β-strands that form a β-sheet with the one β-strand of the substrate. This β-sheet is in close proximity with the active site, and guides the process of catalysis.<ref name="Zhou">PMID:30630874</ref> | ||
