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Relative to the inactive GLP-1R 30 , this includes an upwards and clockwise rotation of the ECD relative to the TMD, a reorganisation of the extracellular TM regions to accommodate peptide engagement and rearrangement of a conserved central polar network to stabilise a sharp kink within the centre of TM6, which facilitates the large outward movement of this TM at the intracellular face that is required to accommodate G protein binding