According to the literature, the autoantigen La is involved in Cap-independent translation.
It was proposed that one prerequisite for this function is the formation of a protein
dimer. However, structural analyses argue against La protein dimers. Noteworthy to
mention, these structural analyses were performed under reducing conditions. Here
we describe that La protein can undergo redox-dependent structural changes. The oxidized
form of La protein can form dimers, oligomers and even polymers stabilized by disulfide
bridges. The primary sequence of La protein contains three cysteine residues. Only
after mutation of all three cysteine residues to alanine La protein becomes insensitive
to oxidation, indicating that all three cysteines are involved in redox-dependent
structural changes. Biophysical analyses of the secondary structure of La protein
support the redox-dependent conformational changes. Moreover, we identified monoclonal
anti-La antibodies (anti-La mAbs) that react with either the reduced or oxidized form
of La protein. Differential reactivities to the reduced and oxidized form of La protein
were also found in anti-La sera of autoimmune patients.
