Conformational Flexibility of a Lipocalin Allergen (Mus m 1): Implications for Molecular Allergy Diagnostics

TL;DR

This paper studies how changes in a mouse allergen protein affect its structure and stability, which could help develop better allergy diagnostics and treatments.

Contribution

The study identifies a specific mutation (C138A) that increases the stability and allergenic potential of the Mus m 1 protein.

Findings

The C138A mutation reduces solvent-accessible surface area and α-helix displacement, increasing folding stability.

The C138A mutant maintains allergenic potential and is a promising candidate for diagnostics and vaccines.

MD simulations and HINT analysis revealed structural insights into how mutations affect protein dynamics.

Abstract

Mus m 1 lipocalin is the cause of mouse allergy in sensitized individuals. The production of a soluble, stable, and immunogenic isoform of Mus m 1 is essential for developing new diagnostic tools and immunotherapeutic protocols for treating allergic symptoms. To that end, using molecular dynamics (MD), we explored the impact of substitutions at positions 120 and 138 on the structure and dynamics of the allergic isoform Mus m 1.0102. HINT-based analysis of the MD trajectories, obtained for the mutants Y120F, Y120A, C138S, and C138A, allowed the assessment of the mutations’ impact on the network of intramolecular interactions, providing insights into the mechanisms underlying protein stability, dynamics, and allergenic reactivity. The C138A mutant revealed a reduction in the solvent-accessible surface area in the region of the mutated residue, of the radius of gyration, and of the α-helix displacement from the β-barrel, features that correlate with an increase in folding stability and a satisfactory allergenic potential. We consider C138A a good candidate to be exploited for diagnostic and vaccine purposes.

Figures