The ‘Rapunzel’ virus has a bizarre long tail and we finally know why: ScienceAlert

For billions of years, viruses and bacteria have been locked in a never-ending arms race, and it has resulted in one predator becoming “a monster of a tail.”

The unique bacteria-devouring virusor bacteriophage, is officially called P74-26, although it is more popularly known as the ‘Rapunzel’ virus.

Like the absurdly long locks of the fairytale princess, the pathogen’s “ponytail” stands out in a crowd of its ilk.

At nearly a micrometer in length, the appendage is 10 times longer than most other bacteriophages.

In fact, it has the longest tail of all known viruses and, oddly enough, also the most stable.

Rapunzel virus tail
P74-26 tail compared to most other phage tails. (Agnello et al., Journal of Biological Chemistry, 2023)

According to new research, this impressive appendage is likely what makes the Rapunzel possible virus to find and pierce one of the strongest bacteria on Earth in one of the most inhospitable environments.

In bubbling hot springs that reach temperatures well above 77°C (170°F), the Rapunzel virus lives by infecting the bacteria Thermus thermophilus and use the other cell’s machinery to reproduce and multiply.

By stitching together many images of the virus’s tail at different points of its construction, scientists were able to unravel its unique structure. Computer simulations further elucidated the “highly intertwined network of interactions” that coordinates to build this impressively long probe.

“We used a technique called cryo-electron microscopy, which is a huge microscope that allows us to take thousands of pictures and short films at very high magnification,” explains microbiologist Emily Agnello of the University of Massachusetts (UMass) Chan Medical School.

“By taking a lot of pictures of the phage’s tail tubes and stacking them on top of each other, we were able to figure out exactly how the building blocks fit together.”

Bacteriophage tails come in a variety of lengths and styles: some long, some elastic, some short, and some stiff. These molecular ‘machines’ have evolved to recognize specific bacterial host cells before penetrating them and then deliver their genome to the cytoplasm for replication.

Given the lock-and-key nature of this attack, there is a wide diversity of tails among bacteriophages, found in virtually every habitat on Earth. But how exactly do these tails differ?

To date, scientists have characterized very few phage-host interactions, and with antibiotic resistance a growing threat to human health, experts are turning to phages for ideas on how to defeat superbugs.

For example the Rapunzel virusThe tail seems to be such a threat to bacteria because of the way its building blocks interlock and stack up.

Despite its massive size, the virus‘s tail relies on half the number of building blocks as other bacteriophages, researchers say, and that seems to make all the difference.

“We think what happened is something old virus its building blocks fused together into one protein,” says UMass biochemist Brian Kelch.

“Imagine two small Lego bricks being fused into one big brick with no seams. This long tail is built with larger, sturdier building blocks. We think that could stabilize the tail at high temperatures.”

Illustration of the Rapunzel virus
Illustration of the Rapunzel virus. (Leonora Martinez-Nunez)

These extra sturdy sub-units stack with a ‘ball-and-bowl’ like mechanism similar to Lego bricks, with one side studded and the other in a pocket.

In viruses, each of these building blocks has a sort of ring-like shape, meaning that the entire tail forms a hollow tube when completed. This is the channel through which the virus directs its genome once it has entered a bacterial cell.

“Our research shows that these building blocks can change shape or conformation when they come together,” says Agnello.

“This shape-shifting behavior is important for the building blocks to fit together and form the proper structure of the tailtube.”

The Rapunzel virus tail is exceptionally long, which seems to give it extra strength in sticking to and entering bacteria. At the same time, however, that enormous length means that there is more chance that the tail assembly goes wrong.

Researchers think there must be internal mechanisms that keep the developing tail on the right path, and these mechanisms are likely shared with other phages.

Understanding how they work could one day help scientists develop better treatments to fight deadly bacteria.

“I believe that studying unique, interesting things can lead to findings and applications that we can’t even imagine yet,” says Agnello.

Now that they know how the virus‘tail shapes, researchers plan to genetically alter the length to see how that might alter interactions with bacteria.

Regardless of the outcome, these experiments are sure to teach us something new.

The research has been published in the Journal of biological chemistry.

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