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The functions of sites-1 and −2 insulin binding. (a) Site-1 insulin plays a critical role in insulin-induced IR activation by breaking the auto-inhibited conformation of IR and by stabilizing the active conformation. (b) Site-2 insulin plays an auxiliary role in insulin-induced IR activation by assisting site-1 insulin to break the auto-inhibited conformation of IR and by preventing the formation of asymmetric IR.
