Figure 2.

Receptor-bound structures of insulin and IGF-1 and NMR structure of IGF-2. A, cryo-EM structure of IR-A–bound insulin (PDB code 6HN5 from Ref. 22, in light brown). Receptor site 1′ is represented by the L1 domain (light gray), and αCT peptide (dark gray) and receptor site 2′ are represented by the FnIII-1 domain (light gray). B, crystal structure of IGF-1 (PDB code 5U8Q from Ref. 19, in violet) bound to L1 domain (in light gray) and αCT (in dark gray) representing site 1′ of IGF-1R. C, NMR structure of human IGF-2 (PDB code 5L3L from Ref. 26, in green). The side chains of residues modified in this study are shown as sticks and are numbered.