Sandbox Reserved 1719: Difference between revisions
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Canonically, the conserved PIF motif consists of a Pro, Ile, and Phe that transduce the signal produce by ligand binding through the TMD within conserved distances.<ref name="Can"/><ref>DOI: 10.1038/s41467-017-02257-x</ref> | Canonically, the conserved PIF motif consists of a Pro, Ile, and Phe that transduce the signal produce by ligand binding through the TMD within conserved distances.<ref name="Can"/><ref>DOI: 10.1038/s41467-017-02257-x</ref> | ||
In MRGPRX2, the PIF motif is changed to a <scene name='90/904324/Pifllf_motif/5'>LLF motif</scene>, in which the residues are shifted down, so that the specific amino acid sequence is not conserved, but instead are conserved at distances that allow them to interact.<ref name="Can"/> Specifically, the residues that make up TM5 have shifted down two residues making Leu194 analogous to the position of the Pro in other GPCRs. However, one key difference is that Leu194 is positioned closer (5.48Å) than the conserved distance (5.50Å).<ref name="Can"/> Leu194 is involved in this motif because the residue that is at the canonical distance is angled away from the TM3-TM6 interface, so it | In MRGPRX2, the PIF motif is changed to a <scene name='90/904324/Pifllf_motif/5'>LLF motif</scene>, in which the residues are shifted down, so that the specific amino acid sequence is not conserved, but instead are conserved at distances that allow them to interact.<ref name="Can"/> Specifically, the residues that make up TM5 have shifted down two residues making Leu194 analogous to the position of the Pro in other GPCRs. However, one key difference is that Leu194 is positioned closer (5.48Å) than the conserved distance (5.50Å).<ref name="Can"/> Leu194 is involved in this motif, despite the closer positioning, because the residue that is at the canonical distance is angled away from the TM3-TM6 interface, so it is unable to interact.<ref name="Can"/> Compared with other structures, such as [https://proteopedia.org/wiki/index.php/5-hydroxytryptamine_receptor 5-HT<sub>2A</sub>R], [https://proteopedia.org/wiki/index.php/Adrenergic_receptor A<sub>2A</sub>R], and [https://proteopedia.org/wiki/index.php/Beta-2_Adrenergic_Receptor β<sub>2</sub>AR], the TM6 helix of MRGPRX2 is closer to the TM3 helix due to the shift in residues, which accounts for the tighter packing of the transmembrane domain helices<ref name="Can"/>, thereby contributing to surface level ligand interactions. | ||
=== DRY/ERC motif === | === DRY/ERC motif === | ||
