The Anthrax Toxin Lethal Factor in Solution Does Not Have the Protein's Crystallized Structure.

Area of Science:

• Biochemistry
• Structural Biology
• Microbiology

Background:

• Bacillus anthracis secretes exotoxins, including Lethal Factor (LF), Protective Antigen (PA), and Edema Factor (EF).
• PA83, cleaved to PA63, facilitates LF and EF entry into host cells, causing cell death.
• Numerous crystal structures of LF exist in the Protein Data Bank, primarily showing congruent monomeric or bound forms.

Purpose of the Study:

• To determine the solution structure of Bacillus anthracis Lethal Factor (LF) using small-angle neutron scattering (SANS).
• To compare the solution structure of LF with its known crystal structures.
• To assess the feasibility of predicting solution structures from crystal data.

Main Methods:

• Small-angle neutron scattering (SANS) was employed to measure the equilibrium structure of LF in D2O solution.
• The scattering data was modeled using a parallelepiped shape to determine molecular dimensions.
• Crystal structure data (PDB 1pwu) was also modeled for comparison.

Main Results:

• The solution structure of LF was best modeled by a parallelepiped with dimensions 12 Å × 49 Å × 129 Å.
• This solution shape significantly differs from the dimensions derived from the crystal structure (30 Å × 48 Å × 104 Å).
• The calculated molecular weight from the solution structure is consistent with the known monomeric weight of LF.

Conclusions:

• The solution structure of LF exhibits substantial dimensional differences compared to its crystal structure.
• Direct physical modeling of solution structure from crystal forms is insufficient to accurately represent LF's state in solution.
• These findings highlight the importance of solution-based structural studies for understanding protein function in biological contexts.