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Agonist-induced formation of unproductive receptor-G12 complexes

Mounted on the membrane-facing surface of the cytoplasmic tip of TM6, compound 2 was able to induce a newly discovered ECD conformation allowing its N-terminal helix to penetrate into the TMD core, a key step for the ago-allosterism observed experimentally, consistent with the intrinsic agonism hypothesis for the ECD of GLP-1R 40