Vision starts with a turbo chemical reaction in the eyes
CIFAR researchers have discovered that the first molecular reaction in vision generation happens much faster than any previously known biological process, occurring at the very limits of what is theoretically possible in biological functions.
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 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 of CIFAR Senior Fellows R. J. Dwayne Miller (University of Toronto and Max Planck Institute for the Structure and Dynamics of Matter) and Oliver P. Ernst (University of Toronto) 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.
“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 program Molecular Architecture of Life, which is untangling the details of the complex molecular processes that underlie all living systems.
The research was published in Nature Chemistry Nov. 16.
This research was supported by the Max Planck Society, the Natural Sciences and Engineering Research Council of Canada (NSERC) and the Canada Excellence Research Chairs program (CERC).
Image: An artistic impression of the molecular motion of the retinal chromophore leading to sight. Credit: © J.M. Harms, MPSD
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