Crystal structure and its proposed nucleolytic site of the single domain catalytic antibody 3D8-VH

다국어 초록 (Multilingual Abstract)

Catalytic antibodies are monoclonal antibodies with catalytic activities. An anti-DNA antibody can bind DNA and hydrolyzeit with modest catalytic activity. The monoclonal antibody 3D8 from the autoimmune-disease prone MRL-lpr/lpr mouse hasbeen used to make a recombinant single-chain variable-fragment antibody (3D8 scFv) that hydrolyzes DNA. The catalyticsite is composed of several hyper-variable loops. Two His residues from the variable domains of the heavy chain (VH) andthe light chain (VL) are responsible for DNA hydrolysis. Interestingly, two single domain antibodies derived from 3D8 scFv,called 3D8-VH and 3D8-VL, also bind and hydrolyze DNA although their activities are significantly lower than those of 3D8scFv. Here, we report the crystal structure of 3D8-VH, which revealed no significant difference compared to the VH domainfrom 3D8 scFv. The 3D8-VH antibody is also structurally very similar to 3D8-VL that has a catalytic metal ion on the newlyexposed surface-curvature. The observed structural features of 3D8-VH, along with the fact that it retained catalytic activitywhen the His residue that was catalytic in the 3D8 scFv was replaced, suggest that 3D8-VH also has its DNA bindingand cleavage activity on the newly exposed surface. These findings provide new insights into substrate recognition andcatalysis by single domain anti-DNA antibodies.

참고문헌 (Reference)

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