Abstract
Regulatory factor X (RFX) proteins are transcriptional activators that recognize X-boxes (DNA of the sequence 5′-GTNRCC(0–3N)RGYAAC-3′, where N is any nucleotide, R is a purine and Y is a pyrimidine) using a highly conserved 76-residue DNA-binding domain (DBD). DNA-binding defects in the protein RFX5 cause bare lymphocyte syndrome or major histocompatibility antigen class II deficiency1. RFX1, -2 and -3 regulate expression of other medically important gene products (for example, interleukin-5 receptor α chain, IL-5Rα)2. Fusions of the ligand-binding domain of the oestrogen receptor with the DBD of RFX4 occur in some human breast tumours3. Here we present a 1.5 Å-resolution structure of two copies of the DBD of human RFX1 (hRFX1) binding cooperatively to a symmetrical X-box4,5. hRFX1 is an unusual member of the winged-helix subfamily of helix–turn–helix proteins6 because it uses a β-hairpin (or wing) to recognize DNA instead of the recognition helix typical of helix–turn–helix proteins. A new model for interactions between linker histones and DNA is proposed.
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Acknowledgements
We thank D. Thiel and the MacCHESS staff, and Z. Dauter and K.R. Rajashankar and the NSLS X9B staff for help with X-ray data collection. We thank C. Lenoir for assistance in peptide synthesis, and J. Bonanno, K. L. Clark, J. E. Darnell, R. C. Deo, D. Jeruzalmi, J. Kuriyan, E. Lai, H. A. Lewis, S. K. Nair and G. A. Petsko for many useful discussions. S.K.B. is an Investigator in the Howard Hughes Medical Institute. This work was supported by the National Institute of General Medical Sciences.
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Gajiwala, K., Chen, H., Cornille, F. et al. Structure of the winged-helix protein hRFX1 reveals a new mode of DNA binding. Nature 403, 916–921 (2000). https://doi.org/10.1038/35002634
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DOI: https://doi.org/10.1038/35002634
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