Download MendeleyStructure of the winged-helix protein hRFX1 reveals a new mode of DNA binding.
Gajiwala, K.S., Chen, H., Cornille, F., Roques, B.P., Reith, W., Mach, B., Burley, S.K.(2000) Nature 403: 916-921
- PubMed: 10706293
- DOI: https://doi.org/10.1038/35002634
- Primary Citation of Related Structures:
1DP7 - PubMed 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 deficiency. RFX1, -2 and -3 regulate expression of other medically important gene products (for example, interleukin-5 receptor alpha chain, IL-5R alpha). Fusions of the ligand-binding domain of the oestrogen receptor with the DBD of RFX4 occur in some human breast tumours. Here we present a 1.5 A-resolution structure of two copies of the DBD of human RFX1 (hRFX1) binding cooperatively to a symmetrical X-box. hRFX1 is an unusual member of the winged-helix subfamily of helix-turn-helix proteins because it uses a beta-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.
Organizational Affiliation:
Laboratories of Molecular Biophysics, Pels Family Center for Biochemistry and Structural Biology, The Rockefeller University, New York, New York 10021, USA.
