Research findings recently published in Nature Chemistry magazine have shown that the first molecular reaction in vision generation happens much faster than any previously known biological process, occurring at the very limits of speeds theoretically possible in biological functions.

The research was co-led by Oliver Ernst, Canada Excellence Research Chair in Structural Neurobiology at the University of Toronto, and R. J. Dwayne Miller, who is also at the University of Toronto. Both are Canadian Institute for Advanced Research senior fellows.

A version of the following article about the discovery first appeared on the CIFAR website:

The first steps of vision take place in specialized cells in our eyes called photoreceptors. The pigment in these photoreceptors is called rhodopsin, which consists of the protein opsin and the chromophore retinal. When light hits rhodopsin it causes an isomerization reaction in the retinal that changes the shape of the chromophore and of the entire protein, enabling the rhodopsin to interact with other proteins and initiating the visual signaling cascade that ultimately sends an electrical signal to the brain.

Although scientists understand retinal isomerization in some detail, how long the entire process actually takes remained elusive. With the help of an advanced type of spectroscopy called heterodyne-detected transient grating spectroscopy—a kind of holography in which the molecular motions are recorded in time—the teams led by Ernst and Miller investigated retinal isomerization within bovine rhodopsin.

The researchers found that the process takes place in 30 femtoseconds, or 30 millionths of a billionth of a second. Previously, the best measurement suggested it took place in 200 femtoseconds, nearly an order of magnitude slower. The ultrafast speed seems to represent a molecular speed limit.

“It simply could not happen faster. Thirty femtoseconds is a new speed record for chemistry, especially for such a complex system,” Miller says.

The researchers also found that the vibrational motions of the molecules—a process of stretching, twisting and wagging—help direct the chemical reaction. The molecules move in such a way that they bring different atoms into contact at just the right time for the necessary interactions. Of thousands of possible motions, only the two or three that were needed to drive the process kicked in.

Oliver Ernst
Canada Excellence Research Chair in Structural Neurobiology

“The atomic motions are all perfectly choreographed by the protein. It is amazing,” says Miller. “This is the first step in optimization of molecular responses that is important to cell functions. Rhodopsin provides a model system of how cells get information and store energy at the molecular level.”

Ernst says, “The findings of how retinal and protein interact will be important for helping us zoom in on the most critical details of how molecular receptors have been optimized to recognize chemical signal molecules, that is, to receive information precisely and relay it onward, in this case to our brains, where we process images.”

Rhodopsins belong to the class of so-called G-protein-coupled receptors that sense a huge variety of chemical signals, including hormones and neurotransmitters. Dysfunctional G-protein-coupled receptors are implicated in diseases that cause vision loss, heart failure, metabolic syndrome, schizophrenia, epilepsy, pain, cancer, fertility disorders and many other conditions. About 50 per cent of current drugs are estimated to be related to diseases involving G-protein-coupled receptors.

Miller and Ernst are co-directors of CIFAR’s Molecular Architecture of Life program, which is untangling the details of the complex molecular processes that underlie all living systems.

The research was supported by the Canada Excellence Research Chairs Program, CIFAR, the Max Planck Society, and the Natural Sciences and Engineering Research Council.