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It is known that two highly conserved polar networks at the cytoplasmic face of class B1 GPCRs, the HETY network (H 2.50b E 3.50b T 6.42b Y 7.57b ) and the cytoplasmic polar network (R 2.46b R 6.37b N 7.61b E 8.49b ), lock the base of the receptor in a closed conformation 19

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