Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Atomic-resolution views suggest function of enzyme that regulates light-detecting signals in eye

09.10.2008
Enzyme undergoes large conformational change after small messenger molecule binds

An atomic-resolution view of an enzyme found only in the eye has given researchers at the University of Washington (UW) clues about how this enzyme, essential to vision, is activated. The enzyme, phosphodiesterase 6 (PDE6), is central to the way light entering the retina is converted into a cascade of signals to the brain.

This particular form of the enzyme comes from the cone photoreceptors of the retina and has not been well-researched, in contrast to its rod form. Rods are involved in night vision and motion sensation; the cones are responsible for color sensitivity, visual acuity, daylight vision, and adjustment to bright light.

The section of the enzyme molecule that most interests the researchers is the so-called GAF A domain. A small messenger molecule, cGMP, binds to the GAF A domain to regulate the enzyme.

"The domain binds to this small molecule with extremely high sensitivity," said UW biochemist Clemens Heikaus, who along with Sergio E. Martinez, now a research associate at Rutgers, carried out the study. "From our structure, we can infer why it prefers cGMP over other messenger molecules." He added that the domain is quick in recognizing and responding to the messenger molecule to create an instantaneous flow of information to the brain.

Using X-ray crystallography and nuclear magnetic resonance, the researchers discovered that the enzyme undergoes major structural changes upon binding of the cGMP molecule.

Before binding occurs, the GAF domain is like an outstretched palm with the fingers wiggling, Heikaus said. After the cGMP molecule binds, the GAF domain closes and becomes less dynamic. In this state it looks more like a closed fist.

Further analysis of the consequences of this conformational change may lead to a better understanding of how the photoreceptor PDE helps regulate the path of signals that enable us to see, as well as provide general information on proteins with GAF domains.

"The addition of a simple, small molecule to the GAF domain affects the entire PDE enzyme," Heikaus said. Researchers think the binding to the domain may act as a switch that turns on the enzyme.

The research findings were published in the Sept. 19 Journal of Biological Chemistry. The article was selected as a Paper of the Week. The journal cover featured a striking image of the iris of Heikaus' eye, photographed by UW ophthalmology imaging supervisor Brad Clifton. Superimposed in the center of the pupil was a three-dimensional structure of the GAF domain.

In humans, GAF-containing proteins are rare. In plants and bacteria, GAF domains are widespread and are specialized for binding a variety of molecules. Some of these plant and bacteria GAF domains are important in detecting light, but they do so through a mechanism that is completely different from vision in vertebrate animals.

GAF domains emerged more than 3 billion years ago in early forms of life, and remained as animals and humans evolved, a phenomenon evolutionary biologists call conservation. Human GAF domains have similar protein folds, and a similar way of binding signal-triggering molecules inside a "pocket," as do GAF domains in more primitive creatures.

Humans have only a few kinds of GAF domains, all of which are in enzymes within the PDE family. They perform important functions not only in vision but also in hearts, lungs, and blood vessels. PDE5, an enzyme closely related to PDE6, is the therapeutic target for sildenafil, known by the trade name Viagra. In some men, this drug also inhibits PDE6 in the eyes, causing a temporary change in color vision.

More knowledge of the basic mechanisms of PDEs in vision may lead someday to better drug treatment for loss of eyesight from damaged retinas, such as occurs in night blindness and retinitis pigmentosa.

Leila Gray | EurekAlert!
Further information:
http://www.washington.edu

More articles from Life Sciences:

nachricht Link Discovered between Immune System, Brain Structure and Memory
26.04.2017 | Universität Basel

nachricht Researchers develop eco-friendly, 4-in-1 catalyst
25.04.2017 | Brown University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

Link Discovered between Immune System, Brain Structure and Memory

26.04.2017 | Life Sciences

New survey hints at exotic origin for the Cold Spot

26.04.2017 | Physics and Astronomy

NASA examines newly formed Tropical Depression 3W in 3-D

26.04.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>