Bringing Structure to Biology
Opening up a Wormhole
The image for September in our 2018 calendar depicts Lysenin, a molecular hole punch produced by garden earthworms.
Revealing Beautiful Biology
Earthworms produce lysenin as an immune mechanism. It helps protect the worm from infection by boring holes in the cell membrane of organisms pathogenic to the worm, causing the cell contents to leak out.
Lysenin is a member of the small ß-pore-forming toxin family, so named due to the ß-strands (depicted as arrows in the artwork) that come together to punch a hole through the cell membrane of the target cells. While the worm uses lysenin to protect it against infection, many members of this protein family are instead found in bacteria which cause infection in humans; in these cases, lysenin molecules are involved in the infection process. Some examples include aerolysin protein produced by Aeromonas spp, as well as epsilon toxin protein and α-toxin protein, both from Clostridium perfringens.
Like all members of the family, lysenin is secreted as inactive, water-soluble monomers. On binding to specific lipids or proteins in the target cell membrane, the protein then undergoes significant structural rearrangement (much like a transformer toy!) and along with other lysenin molecules forms a pre-pore, and finally a full pore in the cellular membrane.
Cutting Edge Science
The method used to solve this structure was Cryo-electron microscopy (CryoEM). For on more information on the technique used, you can view this description by leading CryoEM scientist Gabe Lander. In addition to using this protocol, the scientists who worked on lysenin also immobilized the protein onto the small copper microscope grid using a graphene oxide layer, rather than carbon which is standard. At the time of this experiment, this method was critical solve the structure to such high resolution.
Inspiring Thoughtful Art
The artwork to the left is the work of VyWien Lai a student from The Leys school in Cambridge. She explained “I am showing the protein being sucked into a vortex. I have used colours to illustrate the movement as the protein punches holes in cell membranes.”
written by Alice Clark