Anyone who's spent time at a beach on a warm summer night has seen them: luminescing ctenophores that twinkle like tiny stars in moonlit waters. No one knows exactly why these comb jellies flicker and glow, but Marine Biological Laboratory (Cape Cod, Massachusetts) senior scientist Osamu Shimomura now knows a lot more about the structure of the remarkable protein that is not only responsible for this phenomenon, but has proved to be an invaluable tool for researchers studying the role of calcium in disease.
In this week's issue of the journal Nature, Shimomura and his colleagues James Head from Boston University, Katsunori Teranishi from Mei University (Japan), and Satoshi Inouye from Chisso Corporation (Japan), describe the three-dimensional crystal structure of aequorin, the photoprotein that illuminates jellyfish, ctenophores and many other luminescing organisms. The study was supported by the National Science Foundation.
"The work of these investigators has clearly demonstrated how insights into the structure of a protein lead to insights into its biological function...with great potential for molecular modeling and designing new sensors for monitoring other ions in a cell," according to Ralph Addison, program director in NSF's biophysics program, which supported this work.
Since his discovery of aequorin 38 years ago, Shimomura's life's work has been devoted to shedding light on luminescence-a complex chemical reaction within an organism's cells that results in the release of energy in the form of light instead of heat. Shimomura determined years ago that aequorin glows blue when tiny amounts of calcium bind to it.
This discovery led to the use of aequorin as an important biomedical tool for tracking the movement of calcium within cells. Calcium plays a crucial role in the regulation of a variety of biological processes including fertilization, muscle contraction, and the transmission of nerve impulses. Clinicians also recognize that calcium is significant in the pathology of a number of neurological diseases, including Alzheimer's.
Much has been learned over the years about aequorin and its regenerated form, apoaequorin. But, says Shimomura, "We've been working blind for many years." Until now, no one has been able to visualize the actual three-dimensional crystal structure of this important protein, something Osamu Shimomura has dreamed of doing since first discovering aequorin.
Now that Shimomura and his colleagues know the exact structure of aequorin, they'll be better able to study how the protein functions in concert with other chemicals, and, possibly, enhance its usefulness as a biological marker.
"One of the most exciting outcomes of knowing the structure of aequorin is that it offers the potential for us to perhaps 'custom' design molecules that are able to sense different molecules or ions," explains co-author James Head of Boston University. "These would then 'wink' at us, with light emission, when a certain molecule is encountered. It is possible that, based on the current structure, we may be able to engineer the protein to respond to different ions at different ranges of concentrations, and conceivably combine the aequorin structure with other protein domains that bind entirely different molecules to produce completely new sensors. This has the potential to provide a family of biosensors for use in biological systems, and, under the right conditions, possibly also for use in industrial settings."
Media contact: Pam Clapp, MBL
508-289-7423
pclapp@mbl.edu
Program contact: Ralph Addison
703-306-1442
raddison@nsf.gov