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The allergen Mus m 1.0102: Cysteine residues and molecular allergology
The allergen Mus m 1.0102: Cysteine residues and molecular allergology
- Source :
- Molecular Immunology. 120:1-12
- Publication Year :
- 2020
- Publisher :
- Elsevier BV, 2020.
-
Abstract
- Mus m 1.0102 is a member of the mouse Major Urinary Protein family, belonging to the Lipocalins superfamily. Major Urinary Proteins (MUPs) are characterized by highly conserved structural motifs. These include a disulphide bond, involved in protein oxidative folding and protein structure stabilization, and a free cysteine residue, substituted by serine only in the pheromonal protein Darcin (MUP20). The free cysteine is recognized as responsible for the onset of inter- or intramolecular thiol/disulphide exchange, an event that favours protein aggregation. Here we show that the substitution of selected cysteine residues modulates Mus m 1.0102 protein folding, fold stability and unfolding reversibility, while maintaining its allergenic potency. Recombinant allergens used for immunotherapy or employed in allergy diagnostic kits require, as essential features, conformational stability, sample homogeneity and proper immunogenicity. In this perspective, recombinant Mus m 1.0102 might appear reasonably adequate as lead molecule because of its allergenic potential and thermal stability. However, its modest resistance to aggregation renders the protein unsuitable for pharmacological preparations. Point mutation is considered a winning strategy. We report that, among the tested mutants, C138A mutant acquires a structure more resistant to thermal stress and less prone to aggregation, two events that act positively on the protein shelf life. Those features make that MUP variant an attractive lead molecule for the development of a diagnostic kit and/or a vaccine.
- Subjects :
- Models, Molecular
0301 basic medicine
Protein Folding
Protein Conformation
Immunology
Immunologic Tests
Protein aggregation
Ligands
Protein Structure, Secondary
Cell Line
Serine
Mice
03 medical and health sciences
0302 clinical medicine
Protein structure
Spectroscopy, Fourier Transform Infrared
Animals
Humans
Cysteine
Structural motif
Molecular Biology
Major urinary proteins
Protein Stability
Chemistry
Oxidative folding
Proteins
Allergens
Recombinant Proteins
Spectrometry, Fluorescence
030104 developmental biology
Amino Acid Substitution
Biochemistry
Mutagenesis, Site-Directed
Protein folding
030215 immunology
Subjects
Details
- ISSN :
- 01615890
- Volume :
- 120
- Database :
- OpenAIRE
- Journal :
- Molecular Immunology
- Accession number :
- edsair.doi.dedup.....24ce57868b484c47d12844b7f8ef05ea
- Full Text :
- https://doi.org/10.1016/j.molimm.2020.01.022