Microtubules are composed of many individual tubulin protein subunits. The subunits form a tube of 13 parallel and slightly staggered columns (protofilaments). (left) When the microtubule breaks down, columns splay apart and peel backwards. The peels then snap off from the disassembling microtubule, break down into smaller pieces, and eventually into individual subunits. (right)

Like the strange, dreamlike underwater world of Jacques Cousteau, particles flow freely, but with purpose, through a liquid atmosphere. Tranquil music further sets the marine-like scene. Eva Nogales's movie uses captivating animation and real molecular structures to offer an eye-opening view of how microtubules—the long protein polymers that help cells divide their genetic material—assemble and disassemble.

Although most biologists are familiar with microtubules, Nogales, an HHMI investigator at the University of California, Berkeley, found that when she described her work to colleagues they had a hard time seeing what she was talking about. Especially when she described how individual protein subunits, called tubulin, add onto a growing microtubule filament or fall away from it.

Then Nogales attended a lecture by one of her Berkeley colleagues in which he played a video of a parasite's life cycle. The movie allowed the audience to observe, and then understand, what her colleague had discovered. She decided to make a movie of her own to convey some of the details that she and her team had discovered through their use of electron microscopy.

In the animation, the Zen-like music underlies Nogales's guiding narration. The viewer is transported along the three-dimensional microtubule polymer, swooping in for close-up views of the building-block tubulin subunits, then panning wide to watch them join the growing end of the microtubule. Three subunits add on to the microtubule, like individual railroad cars joining a waiting train, and the video settles on the mature polymer—a tube of 13 full-length columns.

The researchers believe a tubulin subunit must undergo a subtle change in shape before it can join in the process. They propose that in solution tubulin can have at least two shapes: curved with a kink at the midpoint or straighter. To show how this might work, the filmmakers overlay a colorful crystal structure of the protein backbone on the animated image of a tubulin subunit. As a small nucleotide with two phosphates (guanosine diphosphate, or GDP) drifts off the subunit and one with three phosphates (guanosine triphosphate, or GTP) slides in to replace it, the subunit straightens. Only when it takes on the straighter conformation can it add onto a growing polymer. Once the sheet reaches a critical length, the edges seal together like a zipper closing up a jacket, resulting in a long, tube-shaped microtubule polymer. [Here's where the moving pictures come in handy. See media box below.]

		Computer animation of the disassembly and reassembly of tubulin into microtubules, illustrating the existence of structural intermediates and their relationship to the nucleotide state. Produced for HHMI by Stylus Visuals, Kensington, California. Play Movie...

Images: Nogales Lab

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