Death by Disintegrin

by Joseph DeSisto

Disintegrins. Definitely the coolest-sounding proteins, manufactured by some of the coolest animals, the vipers.

Snake venom contains thousands of different proteins, making it one of the most complex substances in the natural world. Not all of these proteins are toxic, but those that are belong to four major categories, depending on their effects.

Neurotoxins act on your nervous system, which can make for a bad time. Your nerve cells are needed to control muscle movement, and since muscle movement allows you to breath, neurotoxic venom can cause death by paralyzing your ability to do so. Neurotoxins are found in cobras, sea snakes, and their relatives, but seldom in vipers.

Cytotoxins are the good old-fashioned cell-killers, found in many snake venoms. If you get bitten by a venomous snake, these are the proteins that start killing the tissue around the bite. If enough tissue dies on a limb, amputation might be necessary. More often, cytotoxins just make venomous snake bites really, really painful.

A Russell's viper (Daboia russelli) from Bangalore, one of the deadliest vipers in the world. Photo by Sandilya Theuerkauf, licensed under CC BY-SA 2.5.

A Russell’s viper (Daboia russelli) from Bangalore, one of the deadliest vipers in the world. Photo by Sandilya Theuerkauf, licensed under CC BY-SA 2.5.

Hemotoxins are more a viper’s purview, and act on the cardiovascular system. They can destroy red blood cells, prevent the blood from clotting, or just destroy cardiovascular tissue. While neurotoxins are relatively fast-acting, death by hemotoxin is slow. When a mouse or other prey animal is bitten by a viper, it typically runs away for some distance before it succumbs to shock. This presents vipers with a problem — how to track down prey after it has gone off to die? But before we answer that question …

The fourth category, proteases, are proteins that specialize in breaking down other proteins, and viper venom is positively loaded with them. Disintegrins are just one class of proteases, but have many functions. Their primary purpose is to break apart integrin, the stuff animals use to keep their cells stuck together. Disintegrins can also prevent blood from clotting, and have been used in medical research (McLane et al. 2004). Finally, two special disintegrins have a third purpose: they serve as tracking signals that can help the predator find its poisoned prey.

The western diamondback rattlesnake (Crotalus atrox). Photo by Holger Krisp, licensed under CC BY 3.0.

The western diamondback rattlesnake (Crotalus atrox). Photo by Holger Krisp, licensed under CC BY 3.0.

It was only a decade ago that Parker and Kardong (2005) first demonstrated, through a set of experiments, that rattlesnakes (a subfamily of vipers) use airborne scents to relocate their prey after injecting venom. Prior to that, it was thought that rattlesnakes followed a scent trail on the ground. Although experiments had since suggested that rattlesnakes are attracted to prey containing venom, it was unclear just how venom was being used to track prey.

Modern chemistry was the key. Saviola and colleagues (2013) extracted venom from diamondback rattlesnakes, then separated it into some of its major chemical components. With the venom divided, the authors injected each mouse with a different component, then offered these mice to the snakes, as well as mice that had been injected with un-divided venom. Snakes were by far the most responsive to mice that had either been injected with whole venom or with two proteins: crotatroxins 1 and 2, both of which are disintegrins.

So, rattlesnakes don’t merely “smell their own venom” — they smell to a particular pair of compounds, without which they would be unable to find prey after it had been bitten. Vipers very well might not have evolved the bodies, venoms, and life strategies we see today if it had not been for this tiny but crucial adaptation.

The western diamondback rattlesnake (Crotalus atrox) Photo by Clinton & Charles Robertson, licensed under CC BY 2.0.

The western diamondback rattlesnake (Crotalus atrox). Photo by Clinton & Charles Robertson, licensed under CC BY 2.0.

Cited:

McLane M.A., E.E. Sanchez, A. Wong, C. Paquette-Straub, J.C. Perez. 2004. Disintegrins. Current Drug Targets: Cardiovascular and Haematological Disorders 4(4): 327-355.

Parker M.R. and K.V. Kardong. 2005. Rattlesnakes can use airborne cues during post-strike prey relocation. In Mason R.T. et al. (Eds.), Chemical Signals in Vertebrates 10 (397-402). Springer.

Saviola A.J., D. Chiszar, C. Busch, and S.P. Mackessy. 2013. Molecular basis for prey relocation in viperid snakes. BMC Biology 11(20) doi: 10.1186/1741-7007-11-20

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2 responses to “Death by Disintegrin

  1. Pingback: The Milk Adder | Beautiful Nightmares

  2. Pingback: How Poisons Work: Tetrodotoxin | Beautiful Nightmares

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