Solution structure of the DNA- and RPA-binding domain of the human repair factor XPA

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Abstract

The solution structure of the central domain of the human nucleotide excision repair protein XPA, which binds to damaged DNA and replication protein A (RPA), was determined by nuclear magnetic resonance (NMR) spectroscopy. The central domain consists of a zinc-containing subdomain and a C-terminal subdomain. The zinc-containing subdomain has a compact globular structure and is distinct from the zinc-fingers found in transcription factors. The C-terminal subdomain folds into a novel α/β structure with a positively charged superficial cleft. From the NMR spectra of the complexes, DNA and RPA binding surfaces are suggested.

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Figure 1: a Sequence alignment of the central domains of human XPA and other XPAs.
Figure 2: Structures of the zinc-containing subdomain.
Figure 4: a, Distribution of the electrostatic potential (displayed with GRASP31) on the solvent-accessible surface of the central domain of XPA (residues 98–210).
Figure 3: Structures of the C-terminal subdomain.

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Acknowledgements

We thank E.H. Morita, M. Shimizu, T. Shimizu, and M. Maeda for discussions. We thank M. Wäelchli for a critical reading of the manuscript. This work was supported by grants to M.S. and K.T. from the Ministry of Education, Science, and Culture of Japan. M.S. was also supported by the Ciba-Geigy (Japan) Foundation for the Promotion of Science. This work was partly supported by a research grant to K.T. and K.M. from the Human Frontier Science Program.

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Correspondence to Masahiro Shirakawa.

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