3-D atomic view of muscle molecule.

Scientists have known for decades that two proteins called actin and myosin interact to make muscles contract. In muscle cells, these proteins bundle into filaments, with myosin overlying actin and pulling itself along actin to shorten muscle fibers. Myosin obtains the chemical energy needed to fuel this shortening by breaking phosphate off adenosine triphosphate (ATP) molecules.

Now, researchers can take an in-depth look at how this molecular motor frans- forms chemical energy into motion, says Ivan Rayment, a crystallographer at the University of Wisconsin-Madison. In the July 2 SCIENCE, he, Wisconsin colleague Hazel M. Holden, and their collaborators present a detailed, three-dimensional picture of myosin. They then combine their findings with earlier results from the Scripps Research Institute in La jolla, Calif., and from the Max Planck Institute for Medical Research in Heidelberg, Germany "What this work does is tie [previous results] together," says Rayment.

The synthesis confirms current ideas about actin and myosin and fills in some missing details, comments Edwin W. Taylor of the University of Chicago.

"Now you have the 3-D structures of the two major players [actin and myosin]:' adds Ralph G. Yount, a protein biochemist at Washington State University in Pullman. "You can begin to figure out how they work on a molecular basis:'

Until now, the actual structure of the myosin molecule had eluded scientists, Rayment says. Try as they might, they could not grow crystals of this very soluble protein, a necessary first step for doing X-ray diffraction studies to pinpoint the location of the atoms in the myosin molecule.

Then, a decade ago, Rayment modified dissolved myosin by adding methyl side groups to some of the amino acids that make up the protein, thus obtaining crystals. He and his colleagues spent the next six years working out a way to make each myosin molecule in the solution take up the same number of methyl side groups in the same places to ensure that a pure crystal formed.

Myosin consists of two interwoven protein fragments, or "heavy chains:' Each fragment has a fat "head," with two smaller peptide chains attached, and a tail. Rayment's group made crystals of single head fragments.

The new data confirm that one side of myosin's head contains a binding site for ATP. Actin attaches on the opposite side of the head. The structure also shows that the head's two peptide "light chains:' each about 150 amino acids long, cling tightly to the head. Unexpectedly, however, the amino acids in the head also fold to form a cleft along the middle.

"You can now see how the atoms can be interacting and what changes are taking place to [cause] tension:' says Richard W. Lymn, a muscle biophysicist at the National Institute of Arthritis and Musculoskeletal and Skin Diseases in Bethesda, Md.

Rayment and his colleagues think that when ATP attaches, it causes the narrow cleft to widen. This motion splits the binding site for actin and loosens myosin's hold on actin. Then myosin bends, encircles the ATP, and chops off a phosphate. This causes yet another shift in myosin's structure so actin can reattach.

"[This shift] closes the cleft, squeezes out phosphate, and the molecule pops open:' Rayment explains. The initial bending strains the molecule- like stretching a rubber band. The reclosing of the cleft releases that strain, and the rebound of about 5 nanometers causes myosin to slide over actin, creating the "power stroke" for contraction. The light chains extend the distance of this shifting in the cleft, making a longer lever, he adds.

"It's landmark research:' comments Yount. "It's the sort of thing that will wind up in every biology textbook."