Funnel-web spider venom¹ contains powerful neurotoxins that instantly paralyze prey⁴ (usually insects). Millions of years ago, however, this potent⁵ poison was just a hormone⁶ that helped ancestors of these spiders regulate sugar metabolism⁷, similar to the role of insulin in humans. Surprisingly, this hormone's weaponization--described on June 11 in the journal Structure--occurred in arachnids as well as centipedes, but in different ways. Researchers at the University of Queensland in Australia and Lewis & Clark College in Portland, Oregon, made the connection while screening for similarities between the venom proteins and other molecules⁸. They found that even though the toxins³ and the hormone had different genetic⁹ sequences, they had similar molecular¹⁰ shapes.

 

"If you take the sequence of the spider toxin² and you do a BLAST search, the hormone is so different now that you don't pull it out," said study senior author Glenn King, a biochemist and structural¹¹ biologist at the University of Queensland's Institute for Molecular Bioscience. "But when we did a structural search and it pulled up the hormone, that's what really surprised us--the sequence didn't tell us where the toxins evolved from, but the structure did pretty clearly."

 

Knowing a toxin's past is useful for the development of new pharmaceuticals¹² and bioinsecticides. Venom molecules are extremely complex (some are made up of over 3,000 peptides), so once the structure is known, researchers such as King can more easily "evolve" a toxin by making changes to its sequence to add or remove functions. The products of such experiments have yielded blood pressure drugs, analgesics¹³, and bioinsecticides--all organically based and so naturally break down. 

 

King's group found that centipede venom has more subtle alterations¹⁴ of the hormone that make it more stable and therefore a better engineering template. He is collaborating¹⁵ with biological and chemical engineer Jennifer Cochran at Stanford University to conduct these in vitro evolution experiments on the spider and centipede toxins. The goal is to take away their toxicity¹⁶ and find opportunities to use them to solve agricultural or medical problems.

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