Figure 4.

Receptor activation leads to repacking of helices H5–H7 on the TM core of rhodopsin. (a) Inactive structure of rhodopsin. Helices H1–H4 form a scaffold onto which helices H5–H7 pack. The key packing contacts on H5 and H7 are associated with Pro215^5.50 and Pro303^7.50 and their corresponding i-4 carbonyls. Retinal isomerization disrupts both interactions. For H5, the β-ionone ring has a steric clash at the position of the His211^5.46-Glu122^3.37 hydrogen bond upon conversion the all-trans configuration. For H7, the retinal is covalently attached to Lys296^7.43. Upon isomerization, Trp265^6.48 on H6 rotates away from H7 and disrupts a water mediated hydrogen bond with Asn302^7.49, which is part of a hydrogen bonding network stretching from Asn55^1.50 and Asp83^2.50 to the Ala299^7.46 C=O. (b) Overlap of the crystal structures of rhodopsin (1GZM¹⁰, purple) and Meta II (3PQR¹³, light purple) showing the positions of the TM helices. The disruption of the interactions of the His211^5.46 C=O and Ala299^7.46 C=O with the H1–H4 scaffold allows helices H5–H7 to reorient. (c,d) Schematic of the hydrogen bonding changes occurring between inactive rhodopsin and active Meta II rhodopsin.