The Signaling Pathway of Rhodopsin

The signal-​transduction mechanism of rhodopsin was studied by mol. dynamics (MD) simulations of the high-​resoln., inactive structure in an explicit membrane environment. The simulations were employed to calc. equal-​time correlations of the fluctuating interaction energy of residue pairs. The resulting interaction-​correlation matrix was used to det. a network that couples retinal to the cytoplasmic interface, where transducin binds. Two highly conserved motifs, D(E)​RY and NPxxY, were found to have strong interaction correlation with retinal. MD simulations with restraints on each transmembrane helix indicated that the major signal-​transduction pathway involves the interdigitating side chains of helixes VI and VII. The functional roles of specific residues were elucidated by the calcd. effect of retinal isomerization from 11-​cis to all-​trans on the residue-​residue interaction pattern. It is suggested that Glu134 may act as a "signal amplifier" and that Asp83 may introduce a threshold to prevent background noise from activating rhodopsin.