Abstract
We present here the structure of the complex between the CAD domain of caspase activated deoxyribonuclease (CAD) and the CAD domain of its inhibitor (ICAD), determined by nuclear magnetic resonance spectroscopy. The two domains adopt a very similar fold, which consists of an α-helix and a β-sheet, and are aligned side by side in the complex. Notably, the positive charges on the strand β2 at one end of the β-sheet of CAD and negative charges around the opposite end of the β-sheet of ICAD are paired in the complex. Point mutations of the charged amino acids at this interface, on either CAD or ICAD, prevented formation of the functional CAD–ICAD complex. This implies that the interaction between the CAD domains of CAD and ICAD is an essential step in the correct folding of CAD in the complex.
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Acknowledgements
This work was supported in part by Grants-in-Aid from the Ministry of Education, Science, Sports, and Culture in Japan. T.O. and H.S. were supported by research fellowships of the Japan Society for the Promotion of Science.
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Otomo, T., Sakahira, H., Uegaki, K. et al. Structure of the heterodimeric complex between CAD domains of CAD and ICAD. Nat Struct Mol Biol 7, 658–662 (2000). https://doi.org/10.1038/77957
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DOI: https://doi.org/10.1038/77957
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