FIGURE 6.

Mapping of photo contacts and relationship to induced fit. A, schematic model of insulin fit. The insulin monomer is proposed to undergo a change in conformation from its closed unbound state (left) to a more open state (right) in which detachment of the C-terminal B-chain β-strand (residues B24-B28) exposes conserved aliphatic side chains Ile^A2 and Val^A3. B, alternating pattern of photo contacts by the C-terminal B-chain β-strand in which its even-numbered face (Phe^B24 and Tyr^B26) contacts the L1 domain of the IR (α-subunit residues 1-158), whereas the odd-numbered face (Phe^B25 and Thr^B27) contacts the C-terminal insert domain (ID)-derived tail of the α-subunit. C, space-filling model of insulin depicting its front and back surfaces (left and right). Putative L1 contact residues Tyr^B16, Phe^B24, and Tyr^B26 are shown in blue, and insert domain contact residues (Gly^A1, Ile^A2, Val^A3, Glu^A4, Thr^A8, Tyr^A14, Phe^B25, and Thr^B27) are shown in yellow (A2 and A3) or gold. The A-chain is otherwise shown in light gray, and the B-chain in dark gray. D, corresponding molecular surfaces following removal of residues B26-B30 to simulate exposure of Ile^A2 and Val^A3 upon detachment of the C-terminal B-chain β-strand in the hormone-receptor complex. The color code is the same as described for C.