# The Anthrax Toxin Lethal Factor in Solution Does Not Have the Protein’s Crystallized Structure

## TL;DR

This study shows that the structure of the anthrax toxin Lethal Factor in solution differs significantly from its crystallized form.

## Contribution

The paper provides new structural insights into the Lethal Factor toxin in solution using SANS, revealing discrepancies with crystal structures.

## Key findings

- The solution structure of Lethal Factor is best modeled as a 12 Å × 49 Å × 129 Å parallelepiped.
- The crystal structure (PDB 1pwu) does not match the solution structure dimensions.
- Physical modeling of the crystal structure cannot explain the SANS results.

## Abstract

The bacterium Bacillus anthracis secretes three protein exotoxins: Protective Antigen 83 (PA83), Lethal Factor (LF), and Edema Factor (EF). A cleaved form of PA83 (PA63) aids LF and EF entry into the cytoplasm, which leads to anthrax-induced cell death. The Protein Data Bank (PDB) has more than 25 structures of LF: the monomer alone, bound with inhibitors, or bound to PA63. The structures are all—with only minor shifts of a few Ångströms—nearly congruent. We have measured the structure of LF at equilibrium in D2O solution by small-angle neutron scattering (SANS). The shape is modeled well by a parallelepiped (all angles 90°) with dimensions of 12 Å × 49 Å × 129 Å. For a protein with a typical density of 1.4, the molecular weight would be between 55 and 94 kDa, which is comparable to that of the 90.2 kDa monomer. However, the LF crystal structure PDB 1pwu (a generally V-shaped molecule with equal arm lengths ≈ 70 Å) with the same model fits the dimensions 30 Å × 48 Å × 104 Å. Given the large changes in the long and short dimensions, straightforward physical modeling of the solution structure from the crystal form is unable to match the SANS results.