Investigation of interaction between Pax-5 isoforms and thioredoxin using de novo modelling methods.

摘要: Pax-5 transcription factor plays a crucial role in B-cell development, activation and differentiation. In murine B-cells four different isoforms of have been identified, their the regulation activity wild-type protein was revealed although still not fully understood. Using theoretical methods, we investigated properties one region Pax-5e Pax-5d (named UDE domain) present possible model for interaction this domain with thioredoxin that previously postulated based on experimental results. Domain (MW 4.8 kDa) is characterised by an extremely high ratio positively charged residues (8) comparisons to negatively amino acids (3), as well unusually large concentrations prolines (11.6%) cysteines (4.7%). This indicative its protein-protein interaction. The 3D structure either or any analogous sequence yet available, therefore resorted various bioinformatics methods order predict secondary from primary UDE. Physicochemical predicted gave more indication about possibilities UDE-thioredoxin binding. addition, shown both segment NAD-reducing hydrogenase HOXS subunit which believed interact thioredoxin. These studies showed represents ideal binding site developed UDE-TRX complex two disulphide bridges. active remained exposed after could explain unexpectedly resistance isoform oxidation. between can be method transportation into nucleus also vicinity Pax-5a, explaining observed activator Pax-5e.