Anti-DNA autoantibodies: the other DNA-binding proteins Review Article

Using the methods developed to study protein DNA complexes, a small number of workers has begun to characterize the interactions of lupus anti-DNA antibodies with their DNA antigens. These studies indicate that anti-ssDNA generally possess a high affinity for poly(dT) and use aromatic side-chains on complex formation, in common with many previously reported anti-ssDNA, and several DNA-binding proteins. We find that our anti-ssDNA differ from these latter two species in that they are not cross-reactive with non-nucleic acid antigens, unlike many other anti-ssDNA, and their complexation does not appear to be accompanied by significant cation release, as for some DNA-binding proteins. Moreover, in some cases our anti-ssDNA are apparently sequence-specific. Due to the small number of anti-dsDNA mAbs studied, our current understanding of these proteins is limited. However, we have recently obtained a high-resolution crystal structure of 4B2, that reacts with both ss- and dsDNA. This structure should enable us to facilitate mutagenesis experiments to identify the molecular features of dsDNA recognition.