Dynamic spatiotemporal determinants modulate gpcr:g protein coupling selectivity and promiscuity

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SUMMARY

    The authors used the muscarinic acetylcholine receptor M1 (CHRM1) as the test case to determine if modifying the amino_acids at selectivity positions identified for Gs, Gi, and Gq interactions could change the behavior of CHRM1-mediated G protein activation. The authors prioritized contacts from the spatiotemporal code that were identified from G protein family-specific contacts, where amino_acid identity was not conserved in receptors with coupling preference to other G proteins. The authors mutated residues in the CHRM1 to amino_acids found at those same positions in either the ADRB2, HTR1B, or ADORA1 receptors. To . . .

     

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