Specific Recognition of a DNA Immunogen by its Elicited Antibody

SANGUINETI, S., CROWLEY, J.M.C., MERLO, M.F.L., CERUTTI, M.L., WILSON, I.A., GOLDBAUM, F.A., STANFIELD, R. & DE PRAT-GAY, G.

JOURNAL OF MOLECULAR BIOLOGY

ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD

Año: 2007 vol. 370 p. 183 - 195

0022-2836

DNA recognition by antibodies is a key feature of autoimmune diseases yet model systems withstructural information are very limited. The monoclonal antibody ED-10 recognizes one of thestrands of the DNA duplex used in the immunogenic complex. Modifications of the 5? enddecrease the binding affinity and short oligonucleotides retain high binding affinity. We determinedcrystal structures for the Fab bound to a 6mer oligonucleotide containing the specific sequence thatraised the antibody and compared it with the unliganded Fab. Only the first two bases from the 5?end (dTdC) display electron density and we observe 4 key hydrogen bonds at the interface. Thethymine ring is stacked between TrpH50 and TrpH95, and the cytosine ring is packed againstTyrL32. Upon DNA binding, TyrH97 and TrpH95 rearrange to allow subnanomolar binding affinity,five orders of magnitude higher than other complexes, possibly because of having gone throughaffininty maturation in this, the first antibody-DNA immunogen complex described in atomic detail.