Anthrax toxin, popular in bioterrorism is a combination of three distinct proteins titled: protective antigen, edema factor, and lethal factor. The proteins are secreted by Bacillus anthracis, a gram positive, endospore-forming, highly resilient bacterium commonly found in cows and other farm animals. Infected farm animals can pass the toxin to humans through vector transmission via mosquitos or fleas, ingestion of airborne bacterium, or by direct contact with skin. Once inside the body the toxin can cause severe and rapid edema in the lungs, large skin lesions, and can also cause severe gastrointestinal problems.
For this project I will focus on lethal factor, one of the three proteins involved in the toxic mechanism. In short, when the bacterial spores enters humans, the protective antigen protein forms a heptamer cytoplasmic membrane toxin, which acts as a pore, allowing edema factor and lethal factor proteins to enter the cell. Lethal factor, an endoproteinase, then directly interferes with MAPKK signaling resulting in cell death. The protein itself is composed of 776 residues that make up four distinct subunits revealed by X-ray crystallography. In its natural, toxic state, lethal factor consists of a binding domain, a catalytic domain, a catalytic-like domain, and a helix bundle. Of those four domains, domains two, three and four work together to form a grove that can bind to and destroy MAPKK substrates. Even though anthrax toxin is extremely virulent and unique, vaccines and treatments have been discovered using 3D structure analysis of these three proteins thanks to crystallography technology.
Resources For Getting StartedEdit
- EBI multiple-database search results for "Anthrax Lethal Factor"
- MEROPS database entry for Anthrax Lethal Factor
- NCBI GQuery multiple-database search results for Anthrax Lethal Factor
- PDB Molecule of the Month article on Anthrax Lethal Factor
- PDB search results for Anthrax Lethal Factor
- PFAM family: Anthrax-tox_M (PF09156), anthrax toxin lethal factor, middle domain
- Reference amino acid sequence for Anthrax lethal factor
- Reference nucleotide coding sequence of Bacillus anthracis, lethal factor coding sequence
- Wikipedia article on Anthrax Toxin
- Patrick: Anthrax Toxin: Introduction (this page)
- Patrick: Anthrax Toxin: Biological Function
- Patrick: Anthrax Toxin: Biosynthesis
- Patrick: Anthrax Toxin: Gene Sequence
- Patrick: Anthrax Toxin: Amino Acid Sequence and Composition
- Patrick: Anthrax Toxin: Secondary and Tertiary Structure
- Patrick: Anthrax Toxin: Domains and Structural Motifs
- Patrick: Anthrax Toxin: Interactions with macromolecules and small molecules
- Patrick: Anthrax Toxin: Molecular biodiversity and evolution
- Patrick: Anthrax Toxin: PyMOL Images
- Patrick: Anthrax Toxin: Literature Review
- Patrick: Anthrax Toxin: Useful online resources