When we consider the active and inactive structures of a GPCR when describing its activation mechanism, is it sufficient to talk about the change of the distance between TM3-TM6 (macro-switches) and the changes of key motifs such as CWxP, DRY, Na+ pocket, NPxxY and PIF (micro-switches)? Since the GPCR activation mechanism is not yet clearly known (https://doi.org/10.7554/eLife.50279), is it sufficient to compare the structure and activation mechanism of a new GPCR with other structures such as the beta-2 adrenergic receptor when trying to explain its activation mechanism? What can you suggest about this?
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