Behind a beating heart, fingers running fluidly across a piano, or a stomach cell shuffling nutrients to its neighbor are hundreds of motor proteins that make such motion possible. Yet even as biologists have been classifying these proteins and delineating their structures, they have long debated one critical question: How moveth the motors themselves?
Now, a trio of biologists delivers another in a series of jolts to this field. On page 844 , Wei Hua and colleagues Johnson Chung and Jeff Gelles of Brandeis University in Waltham, Massachusetts, dispute the widely accepted mechanism of motion for kinesin, a well-studied member of the motor protein class. The three propose that kinesin, responsible for propelling cellular components and proteins along stiff fibers called microtubules, crawls like an inchworm rather than taking even, symmetrical steps. The theory is striking for, among other issues, its pronouncement that kinesin's two structurally identical heads, clusters of amino acids that do most of the enzyme's work, perform vastly different tasks.
Already the work is prompting sharp words and reflection from those in the motor protein field. Many of our beliefs and the models we've been proposing may turn out to be spectacularly wrong, says Steven Block, a biophysicist at Stanford University in Palo Alto, California, referring not only to the Hua paper but also to a parallel upheaval in the study of myosins, another major group of motor proteins.
Ironically, Gelles's group set out to prove the dominant theory of kinesin movement: that the enzyme's two heads alternately and symmetrically step over each other along the microtubule, a motion known as symmetric hand-over-hand. To attempt to confirm hand-over-hand, the researchers made several adjustments that enabled them to follow individual kinesin molecules, which are normally just 70 nanometers long. First, they anchored kinesin to a glass plate but let the microtubule, a far larger structure to which kinesin is attached, move freely. Second, they slowed the motion of kinesin by restricting its access to energy-providing adenosine triphosphate (ATP). Finally, to amplify minuscule microtubule movements, the group made the connection between kinesin and the plate more rigid.
No spinning around. A microtubule didn't rotate as expected under kinesin's power. 
: W. HUA ET AL. 
When Gelles and colleagues let the motor run, they did not witness the scene they'd expected. Symmetric hand-over-hand demands that each head make a 180 rotation for every 8-nanometer step it takes, says Wei Hua, now at Yale University. But the scientists, whose technology was capable of detecting rotation above 31 , found none at all. The group proposes a new catch-up model for kinesin movement: One head pushes forward 8 nanometers, stops, and drags the second along toward it.
Gelles's team was forced to make a secondary, decidedly unorthodox proposal to make its model fit with a basic rule of kinesin biology: that one ATP energy molecule is burned for every 8-nanometer step. In hand-over-hand, the heads presumably alternate burning, or hydrolyzing, ATP. Here, both heads forge the same 8-nanometer distance each time; therefore, only one head could be hydrolyzing the ATP molecule. The other head, the scientists predict, is chemically inactive while kinesin moves.
That two identical structures could wind up with such divergent jobs is a hotly disputed point of the paper. It's hard to envision how you could relegate [different] functions to the two heads, given that they're produced by the same gene, says Sharyn Endow, a molecular geneticist at Duke University in Durham, North Carolina. Endow and others point to previous work they say shows that both heads hydrolyze ATP. The authors of the new study stand by their story but admit they're as befuddled as everyone else. Maybe there's a reason for [the presence of] two heads that we don't know, says Hua.
Meanwhile, other researchers, such as Joe Howard, director of the Max Planck Institute of Molecular Cell Biology and Genetics in Dresden, Germany, favor yet a third model. In asymmetric hand-over-hand, the kinesin heads step over each other but rotate little. The mystery might be solved if researchers can overcome a technical challenge universal to kinesin motion studies: the difficulty distinguishing between the two tiny heads. Scientists are experimenting with special dyes to do just that.
Myosin researchers can sympathize with their kinesin brethren. Recent work on these motors, which control muscles and transport various proteins, shows that two family members don't move as believed. Myosin VI, whose function remains a puzzle, apparently edges backward and takes far larger steps than its structure suggests is possible. And myosin V has been found to stay stuck to its filament during motion rather than lifting off periodically.
Motor molecules are capable of some pretty surprising things that we might not have predicted, says Richard Cheney, a cell biologist at the University of North Carolina, Chapel Hill. And they're taking scientists along for the roller-coaster ride.

Distinguishing Inchworm and Hand-Over-Hand Processive Kinesin Movement by Neck Rotation Measurements.