Sandbox Ben Whiteside: Difference between revisions
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The <scene name='10/1038819/Amidated_c_term/9'>C-Terminus</scene> of amylin contains an amide group, rather than a carboxylic acid group. This chemical modification allows for more extensive hydrogen bonding to nearby residues, due to the added hydrogen bond donor on the NH2 group. In turn, this allows for favorable hydrogen bonds between S129 of the transmembrane domain and the main chain of Y37 on amylin. This interaction causes a "kink" in the random coil of amylin, displacing Y37 into a hydrophobic pocket, allowing for favorable hydrophobic interactions with W79 of the transmembrane domain. This amidation is thought to be a post-translational modification. <ref name="Vekic">PMID: 36005584</ref> | The <scene name='10/1038819/Amidated_c_term/9'>C-Terminus</scene> of amylin contains an amide group, rather than a carboxylic acid group. This chemical modification allows for more extensive hydrogen bonding to nearby residues, due to the added hydrogen bond donor on the NH2 group. In turn, this allows for favorable hydrogen bonds between S129 of the transmembrane domain and the main chain of Y37 on amylin. This interaction causes a "kink" in the random coil of amylin, displacing Y37 into a hydrophobic pocket, allowing for favorable hydrophobic interactions with W79 of the transmembrane domain. This amidation is thought to be a post-translational modification. <ref name="Vekic">PMID: 36005584</ref> | ||
==== Bypass Motif ==== | ==== Bypass Motif ==== | ||
[[Image:SCT_rAmy_Overlay_v2.png|200 px|left|thumb|Figure 1: Overlay of sCT (orange) without the bypass motif and rAmy containing the bypass motif (green)]] | [[Image:SCT_rAmy_Overlay_v2.png|200 px|left|thumb|Figure 1: Overlay of sCT (orange) without the bypass motif and rAmy containing the bypass motif (green).]] | ||
The <scene name='10/1038869/Bypass_overview/3'>Bypass Motif</scene> is a series of residues in the midsection of the amylin peptide that are crucial for providing structural specificity for the AMYR. Without RAMP association, the CTR is in a relaxed, fluid state, allowing the binding of <scene name='10/1038869/Sct_bypass/1'>Calcitonin</scene>. When RAMP binds the receptor, it is forced into a new, rigid conformation, which interferes with calcitonin binding. Amylin's bypass motif contains a backbone configuration that does not interfere with AMYR, allowing the C-terminus of the peptide to interact with the extracellular domain. The Bypass Motif also binds <scene name='10/1038869/Bypass-ecdl_h-bond/4'>extracellular domain loop 4</scene> and makes <scene name='10/1038869/Bypass-amyr/3'>hydrophobic interactions</scene> with the transmembrane region of AMYR, anchoring the peptide in place for the signaling process to occur. <ref name="Cao">PMID:35324283</ref> | The <scene name='10/1038869/Bypass_overview/3'>Bypass Motif</scene> is a series of residues in the midsection of the amylin peptide that are crucial for providing structural specificity for the AMYR. Without RAMP association, the CTR is in a relaxed, fluid state, allowing the binding of <scene name='10/1038869/Sct_bypass/1'>Calcitonin</scene>. When RAMP binds the receptor, it is forced into a new, rigid conformation, which interferes with calcitonin binding. Amylin's bypass motif contains a backbone configuration that does not interfere with AMYR, allowing the C-terminus of the peptide to interact with the extracellular domain. The Bypass Motif also binds <scene name='10/1038869/Bypass-ecdl_h-bond/4'>extracellular domain loop 4</scene> and makes <scene name='10/1038869/Bypass-amyr/3'>hydrophobic interactions</scene> with the transmembrane region of AMYR, anchoring the peptide in place for the signaling process to occur. <ref name="Cao">PMID:35324283</ref> | ||