Protein’s structure lights the way

In 1961, Osamu Shimomura discovered a light-emitting protein in the jellyfish Aequorea aequorea. Four decades later, Shimomura, now at the Marine Biological Laboratory in Woods Hole, Mass., and his colleagues have finally teased out the crystal structure of this photoprotein, known as aequorin.

Aequorin glows blue when calcium ions bind to it, but it’s more than just a pretty protein. Researchers frequently use it to trace the movement of calcium in cells. Calcium ions regulate many life processes, such as muscle contraction and communication between nerve cells. The details of how aequorin generates its blue light have remained mysterious, however.

New techniques yielding an extraordinarily pure sample of the photoprotein spurred the researchers on their way. The team mapped out aequorin’s three-dimensional molecular structure by analyzing the way crystals of the protein reflect X rays.

Scientists had already figured out the basic chemistry behind aequorin’s glow. A part of aequorin called coelenterazine reacts with oxygen to produce coelenteramide and carbon dioxide, while emitting light. Yet no one knew how coelenterazine fits into aequorin or how calcium participates in the light-emitting reaction.

With the new structure, “we’ve now got an actual picture where we can see how things are arranged,” says coauthor James F. Head of Boston University School of Medicine. “But we’re still speculating on how, when this binds calcium, it goes on to cause the light-emitting reaction.”

Head, Shimomura, and their colleagues report the findings in the May 18 Nature.

Head suggests that the new research could eventually lead to a family of glowing aequorinlike sensors. If scientists knew how to change the photoprotein appropriately, he says, they might be able to engineer new proteins that would emit light when binding other ions, such as lead, zinc, or manganese. Head says that in the more distant future, research might even develop similar photoproteins that glow when encountering more-complex molecules vital to biological processes.

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