Remodeling of a DNA stem-loop by an antigen-binding fragment

BIOL 51

Zhonghui Ou, zhonghuio@gmail.com1, Christopher A. Bottoms2, and John J. Tanner, tannerjj@missouri.edu2. (1) Department of Biochemistry, University of Missouri-Columbia, 117 Schweitzer Hall, University of Missouri, Columbia, MO 65211, (2) Department of Chemistry, University of Missouri-Columbia, 125 Chemistry Bldg, Columbia, MO 65211
DNA-1 and 11F8 are two anti-ss DNA antibodies derived from autoimmune lupus-prone mice. They are very similar to each other in terms of CDR sequence and preference for binding T-rich ssDNA. G1-17 is an oligonucleotide identified by in vitro selection experiments and binds with high affinity and specificity to Fab 11F8. G5-14 is a synthetic oligonucleotide with the ten-nucleotide sequence identical to the stem-loop portion above the bulge of G1-17. The 1.95 angstrom resolution DNA-1/G5-14 structure shows that the two DNA strands dimerize to form a double-stranded DNA dumbbell and have a large conformational change including the breaking and reformation of hydrogen bonds. The most striking feature of the Fab/DNA interactions is the use of extensive PI-PI stacking of the DNA bases and the protein side chains. These results provide insights into the specific recognition model of anti-DNA Abs and the potential challenges in structure based drug design to treat autoimmune diseases.
 

Protein Structure and Folding
4:30 PM-6:30 PM, Sunday, 10 September 2006 Moscone Center -- Hall D, Poster

Division of Biological Chemistry

The 232nd ACS National Meeting, San Francisco, CA, September 10-14, 2006