Protein switch curls bacterial propellers

Without its flagella, many a bacterium would truly be up a creek without a paddle. 

 A bacterium may have a dozen or so of these corkscrew-shaped tails that act as little propellers. A rotary motor protein at the base twirls each flagellum counterclockwise. To change course, a bacterium briefly reverses the flagellar rotation and then tumbles about until heading off in the new direction. 

 This quick switch alters not only the bacterium's path, but the shape of the flagellum as well. Now, an international team of researchers has determined what happens to the complex structure of a flagellum when the bacterium throws its motors into reverse.

 Keiichi Namba of the International Institute for Advanced Research at the Matsushita Electric Industrial Co. in Seika, Japan, and his colleagues have obtained high-resolution, X-ray fiber diffraction patterns of the three-dimensional structure of bacterial flagella. Their images reveal a mechanism that enables a flagellum to switch from its ordinary loose-corkscrew shape, wound in one direction, to a curlier corkscrew wound in the opposite direction.

 The team's report appears in the February Nature Structural Biology.

 The findings represent "a dramatic step forward," says Donald L.D. Caspar of Florida State University in Tallahassee. "The bacterial flagellar system has been one of the most significant models of switching mechanisms in biological structures." 

 A bacterial flagellum is a complex structure made of a bundle of 11 protein strands that wrap gently around each other like the fibers in a rope. In the dramatic change of shape, the strands of a flagellum slide past each other.

 The corkscrew structure arises from the mix of two different types of strands in the bundle. Like mirror-image spiral staircases, one type has an intrinsically left-handed twist and the other a right-handed twist. Bacteria genetically mutated to produce only one type of strand have straight flagella -- which don't make very good propellers, Caspar notes.

 When a normal, corkscrew flagellum reverses rotation, mechanical stress forces the interlocking protein strands to move past each other slightly and fasten together in different spots. "The slipping switch propagates over the entire length of a 10- to 15-micrometer-long flagellar filament within a few tens of milliseconds," says Namba. This speedy shape shift occurs without major rearrangement of the strands, which remain entwined in the same order.

 This subtle slip-and-click mechanism accounts for another observation concerning the lengths of the individual strands. Each strand consists of a chain of protein subunits linked end-to-end like the cars of a train. The subunits in the loose corkscrew flagella are about 0.08 nanometer farther apart than those in the curlier tails. 

 In a conventional scheme of protein refolding, says Caspar, "it's very hard to visualize a structural change in a protein molecule that involves such a small displacement." The current mechanism can account for the tiny change, he adds, because the slippage causes the subunits on neighboring strands to mesh with only a slightly different spacing.

 Namba expects that the switch might also be used in other motor proteins. He says that hemoglobin, the blood molecule that alters its structure when it binds to oxygen, also changes its overall shape without major rearrangements of its components.

 Namba and his colleagues have already obtained even higher resolution images of flagellar filaments, which should show "the atomic detail of the subunit structure and subunit-subunit interactions," he says. "Once the crystal structure is solved and the atomic model is built, we will be able to look into the details of the slipping switch mechanism."