Sandbox Reserved 1701: Difference between revisions
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[[Image:PIF_resized.png|500px|right|thumb|'''Figure 3.''' Conserved PIF motif in 5HT2AR (teal) compared to the LLF motif found in MRGPRX2 (red). Transmembrane helices and residues are numbered and labeled to show how this structural change shifts the orientation of the helices. PDBs: 7s8l and 6wha.]] | [[Image:PIF_resized.png|500px|right|thumb|'''Figure 3.''' Conserved PIF motif in 5HT2AR (teal) compared to the LLF motif found in MRGPRX2 (red). Transmembrane helices and residues are numbered and labeled to show how this structural change shifts the orientation of the helices. PDBs: (MRGPRX2): 7s8l and (5HT2A): 6wha.]] | ||
Another motif found in most, but not all, A family GPCR’s is the PIF motif. The PIF residues (<scene name='90/904305/Llf_motif/5'>Leu-117, Leu-194, and Phe-232</scene>) are found on transmembrane helices 5, 3, and 6, respectively. In MRGPRX2, the PIF motif is changed to LLF residues. '''Figure 3''' shows the conserved PIF motif on 5HT2AR, <scene name='90/904306/Alignment_llf/1'>compared</scene> to the LLF motif on MRGPRX2. This change to LLF shifts helix 6 towards helix 3, and contributes to the tighter packing of helices <ref name="Cao">PMID: 34789874</ref> <ref name="Yang">PMID: 34789875</ref> and therefore a more surface-level ligand binding site. | Another motif found in most, but not all, A family GPCR’s is the PIF motif. The PIF residues (<scene name='90/904305/Llf_motif/5'>Leu-117, Leu-194, and Phe-232</scene>) are found on transmembrane helices 5, 3, and 6, respectively. In MRGPRX2, the PIF motif is changed to LLF residues. '''Figure 3''' shows the conserved PIF motif on 5HT2AR, <scene name='90/904306/Alignment_llf/1'>compared</scene> to the LLF motif on MRGPRX2. This change to LLF shifts helix 6 towards helix 3, and contributes to the tighter packing of helices <ref name="Cao">PMID: 34789874</ref> <ref name="Yang">PMID: 34789875</ref> and therefore a more surface-level ligand binding site. | ||
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=== After Activation === | === After Activation === | ||
After ligand binding and transmembrane protein activation, this signal is transmitted to the alpha subunit of the G-protein which undergoes chemical and conformational changes. The alpha subunit is initially bound with GDP which is then physically replaced by GTP leading to conformational changes. These changes can be seen in this [https://youtu.be/k4fjSZV_-OQ video] of a G-protein alpha subunit activation derived from common rats. This video was constructed by one of the page's authors using PDB files 1bof and 1cip. | After ligand binding and transmembrane protein activation, this signal is transmitted to the alpha subunit of the G-protein which undergoes chemical and conformational changes. The alpha subunit is initially bound with GDP which is then physically replaced by GTP leading to conformational changes. These changes can be seen in this [https://youtu.be/k4fjSZV_-OQ video] of a G-protein alpha subunit activation derived from common rats. This video was constructed by one of the page's authors using PDB files 1bof and 1cip. | ||
[[Image:Screen Shot 2022-03-282 at 6.59.44 PM.png|500px|center|thumb|'''Figure 9.''' Overlay of unbound (transparent) and bound (opaque) transmembrane proteins of both MRGRPX2 (left) and 5-HT2AR (right). PDBs: 7s8l and 6wha.]] | [[Image:Screen Shot 2022-03-282 at 6.59.44 PM.png|500px|center|thumb|'''Figure 9.''' Overlay of unbound (transparent) and bound (opaque) transmembrane proteins of both MRGRPX2 (left) and 5-HT2AR (right). PDBs: (MRGPRX2): 7s8l and (5HT2A): 6wha.]] | ||
=== Clinical Relevance === | === Clinical Relevance === | ||
