2 research outputs found
Retinal Ligand Mobility Explains Internal Hydration and Reconciles Active Rhodopsin Structures
Rhodopsin, the mammalian dim-light
receptor, is one of the best-characterized
G-protein-coupled receptors, a pharmaceutically important class of
membrane proteins that has garnered a great deal of attention because
of the recent availability of structural information. Yet the mechanism
of rhodopsin activation is not fully understood. Here, we use microsecond-scale
all-atom molecular dynamics simulations, validated by solid-state <sup>2</sup>H nuclear magnetic resonance spectroscopy, to understand the
transition between the dark and metarhodopsin I (Meta I) states. Our
analysis of these simulations reveals striking differences in ligand
flexibility between the two states. Retinal is much more dynamic in
Meta I, adopting an elongated conformation similar to that seen in
the recent activelike crystal structures. Surprisingly, this elongation
corresponds to both a dramatic influx of bulk water into the hydrophobic
core of the protein and a concerted transition in the highly conserved
Trp265<sup>6.48</sup> residue. In addition, enhanced ligand flexibility
upon light activation provides an explanation for the different retinal
orientations observed in X-ray crystal structures of active rhodopsin