Figure 6
Structural comparison of the trans isomer with native insulin in its IR site-1 bound and receptor-free forms. (a) Overlay of trans isomer (pink/cyan) with T6 insulin (PDB entry 1MSO, Class 1 (light blue/grey), Class 2 (dark blue/grey)) and with IR site-1 bound insulin (PDB entry 4OGA, gold/grey). Differences in the A2, A3 and A4 side-chain positions arise through rotation of the A1-A8 helix. In the complex this allows accommodation of the IR αCT (not shown). (b) In the IR site-1 bound conformation, insulin’s A1-A8 helix adopts a Class 2 conformation and the A2-A4 residues rotate to enable engagement with IR αCT (dark green), with insulin A3 and A4 residues flanking Asn711 of IR αCT. This conformation and rotation does not occur in trans isomer. Colors are otherwise as in (a).
