Dave Munger - Mimicry at the Molecular Scale

Cool stuff - nature is so damn fascinating. This is from Seed Magazine, which I was sad to learn recently does not exist in paper form any more.

Molecular Mimicry

Research Blogging / by Dave Munger / September 9, 2009

New biological research has revealed mimicry at the molecular scale that could have profound implications for medicine and industry.

Courtesy of John D.

Many of us were first introduced to natural mimics in high school biology class via lessons about the viceroy butterfly, which uses its near-perfect resemblance to the poisonous monarch butterfly to escape predators, or crafty hoverflies, insects that look like bees or wasps, sans nasty sting. But these seemingly harmless examples belie the more sinister functions mimicry serves in the natural world. For instance, ant-mimic spiders prey on other spiders’ babies, scaring the parents off by taking on the appearance and behavior of much more menacing ants.

A July study led by Stephen McMahon describes another less-heralded type of mimicry, a biochemical forgery that can have potentially deadly consequences even for humans. “Dr. Jim,” a research scientist whose blog, Mental Indigestion, strives to “make science more digestible,” explained the research in a blog post last month. This mimicry takes place at the molecular level, when a bacteriophage (a virus that preys on bacteria) known as Tn916 attacks its victims. Normally bacteria are able to defend against the foreign DNA of bacteriophages by attacking and breaking it into pieces. But Tn916 creates a protein that has a similar structure to the bacterium’s own DNA, which means the unlucky microbe cannot mount a defense without damaging itself in the process.

The protein mimic is strikingly compact and elongated, unlike most proteins. It even possesses a hint of a helical structure, just like DNA. When the invading protein’s acidic groups (highlighted in red in the top portion of the figure below) are superimposed on the bacteria’s DNA (the DNA is red and white; the superimposed protein is green and yellow), they match the DNA structure almost perfectly. This clever disguise allows the Tn916 bacteriophage to exploit bacteria’s reproductive systems for its own reproduction. Dr. Jim says the researchers have now identified six additional bacteriophages possessing a similar ability to mimic bacterial DNA. Though such adaptations are apparently rare, they could still present a danger to humans, as they may spread rapidly through ecosystems and promote the emergence of bacterial resistance to antibiotics.

The Tn916 bacteriophage protein (top) resembles bacterial DNA, allowing Tn916 to hijack bacterial cells. At bottom, the green-and-yellow Tn916 protein is superimposed over red-and-white bacterial DNA to highlight their similarity. Image courtesy of James Naismith and David Dryden.

But if nature can play at this mimicry game, humans can, too. One thing natural chemical systems do much better than artificial ones is to catalyze, or speed up, chemical reactions. Honed by eons of natural selection, enzymes in cells hasten processes that would otherwise require thousands of years to occur on their own. What if human scientists could duplicate the structures of enzymes and utilize that power to make their own more efficient catalysts? Michael Clarkson, a post-doc who divides his blogging time between video games and biochemistry, uncovered two papers from David Baker’s laboratory at the University of Washington that document how to do just that.

In one case, Clarkson says, the researchers sped up the Kemp elimination, a process that opens a benzene-ring-like structure in a complex organic molecule. Reactions like this are the building blocks of organic chemistry, allowing researchers to convert one molecule into another and eventually build larger molecules, including drugs and other useful substances. In this case, the researchers actually created an artificial enzyme to mimic a structure frequently found in nature, the TIM barrel. The reaction using the artificial enzyme was faster than the unassisted reaction, but was still much slower than the reaction enabled by a natural enzyme.

More mimicry at Researchblogging.org:

• Should designer genes be patentable? Tom Paine’s Ghost wants to know: If a human designs a gene or other structure mimicking nature, who “owns” it?
• Is she or isn’t she? NeuroDojo takes a closer look: Is the “mimic octopus” misnamed?
• Parasite causes ants to look like berries: GrrlScientist describes a fascinating case of “mimicry” where a parasite’s victim looks like a tasty morsel for birds.

To boost the artificial enzyme’s performance, the team borrowed another trick from nature: They used in vitro evolution, creating randomly varied versions of the manufactured enzyme and promoting the versions that worked best. They ended up with a robust version that improved the speed of the unaided reaction by a factor of 106, a million-fold increase. It’s still not quite as efficient as the best natural enzymes, but it’s an impressive feat nonetheless.

These studies didn’t get a lot of mainstream media coverage, and I’d submit it’s not because they don’t describe important work. The fact is, molecular biology is a difficult subject to convey to the general public. By necessity it’s laden with jargon, and in many cases a PhD is necessary to even have a hope of understanding the raw scientific papers. Properly squeezing such complexity into a minute-long television news story or a 250-word news article is very difficult, if not impossible. That’s why it’s critical for bloggers like Clarkson and Dr. Jim to share this work with the world, in-depth, but ideally still in a way most folks can understand. You can find much more about molecular biology at ResearchBlogging.org.

Dave Munger is editor of ResearchBlogging.org. He also blogs at Cognitive Daily. Each week, he writes about emerging trends in research from across the blogosphere.

Tags: Science, research, biology, Molecular Mimicry, Research Blogging, Dave Munger, Seed Magazine