| Title: | The allergen Mus m 1.0102: Cysteine residues and molecular allergology |
| Author(s): | Ferrari E; Corsini R; Burastero SE; Tanfani F; Spisni A; |
| Address: | "Dept. Medicine and Surgery, University of Parma, via Gramsci 14, 43126, Parma, Italy. Electronic address: elena.ferrari@unipr.it. Dept. Medicine and Surgery, University of Parma, via Gramsci 14, 43126, Parma, Italy. Electronic address: romina.corsini@ausl.re.it. Div. Immunology, IRCCS San Raffaele, Via Olgettina 60, 20132, Milano, Italy. Electronic address: burastero.samuele@hsr.it. Dept. Life and Environmental Sciences, Marche Polytechnic University, via Brecce Bianche, 60131, Ancona, Italy. Electronic address: f.tanfani@univpm.it. Dept. Medicine and Surgery, University of Parma, via Gramsci 14, 43126, Parma, Italy. Electronic address: alberto.spisni@unipr.it" |
| DOI: | 10.1016/j.molimm.2020.01.022 |
| ISSN/ISBN: | 1872-9142 (Electronic) 0161-5890 (Linking) |
| 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" |
| Keywords: | "Allergens/*chemistry/genetics/*immunology Amino Acid Substitution Animals Cell Line Cysteine/chemistry Humans Immunologic Tests Ligands Mice Models, Molecular Mutagenesis, Site-Directed Protein Conformation Protein Folding Protein Stability Protein Struct;" |
| Notes: | "MedlineFerrari, Elena Corsini, Romina Burastero, Samuele E Tanfani, Fabio Spisni, Alberto eng Research Support, Non-U.S. Gov't England 2020/02/12 Mol Immunol. 2020 Apr; 120:1-12. doi: 10.1016/j.molimm.2020.01.022. Epub 2020 Feb 7" |
