Tea and cookies at 3 pm. Seminar starts at 3:15 pm.

Speaker's website: http://www.chem.yale.edu/faculty/yan.html

Abstract: Vertebrate rod and cone pigments are responsible for dim-light and color vision, respectively. They share the same 7-helical transmembrane structure and covalently link to 11-cis retinal, which absorbs a photon to undergo cis-to-trans isomerization to trigger a visual signal. Rod pigment, also known as rhodopsin, can detect photons spanning a 10⁶-fold dynamic range in intensity—and yet be able to detect a single photon. Rhodopsin was evolved from cone pigments to gain photosensitivity for dim-light vision. What are the molecular properties of rhodopsin that was developed during the cone-to-rod evolution to increase photosensitivity? It is known that photosensitivity of visual pigments is limited by dark noise, which is generated by thermal isomerization of 11-cis retinal. Based on the crystal structure of rhodopsin, we hypothesize that an extensive hydrogen-bonding network is responsible for stabilizing the inactive state of rhodopsin to prevent thermal isomerization and lower dark noise. We have obtained experimental evidence to support this hypothesis. First, two mutations of rhodopsin that perturb the hydrogen-bonding network in the retinal binding site dramatically increase the rates of thermal isomerization by 1-2 orders of magnitude. Second, the rates of thermal isomerization of wild-type rhodopsin becomes 2-3 times slower in D₂O than in H₂O, suggesting that the rate-determining step of thermal isomerization involves breaking hydrogen bonds. These results provide insight into understanding the critical role of the extensive hydrogen-bonding network on stabilizing the inactive state of rhodopsin and contribute to our current understanding of molecular evolution of visual pigments. Because the hydrogen-bonding network is formed by residues together with ~20 water molecules in the transmembrane region, our results also reveal the important role of water molecules in the structure and function of membrane proteins.