Evidence for induced fit in antibody-DNA complexes

Anti-DNA autoantibodies (anti-DNA) are a hallmark of the autoimmune disorder systemic lupus erythematosus (SLE). Most subjects with active SLE spontaneously produce antibodies that bind both double-stranded and single-stranded DNA (dsDNA and ssDNA, respectively). Deposition of these anti-DNA-DNA complexes in the kidneys is thought to mediate the tissue injury associated with SLE. However, the elements of DNA that are targeted by anti-DNA have not been identified. One problem in trying to correlate anti-DNA specificity with DNA structure is that binding may be accompanied by conformational changes in polynucleotide ligands, facilitating a better fit to the antibody combining site ("induced fit"). For example, studies of antibody-protein, antibody-peptide, protein-DNA, and protein small molecule complexes show that structural reorganization of ligands can help stabilize biomolecular complex. We have examined the importance of induced fit in anti-DNA-DNA binding and report that monoclonal anti-ssDNA BV04-01, which is typical of anti-DNA in lupus-prone mice, forces structural changes in DNA ligands upon binding.