Structures of the DNA-binding site of Runt-domain transcription regulators.
Runt-domain (RD) proteins are transcription factors that play fundamental roles in various developmental pathways. They bind specifically to DNA sequences of the general form PyGPyGGTPy (Py = pyrimidine), through which they regulate transcription of target genes. The DNA duplex TCTGCGGTC/TGACCGCAG, incorporating the binding site for the RD transcription factors (bold), was crystallized in space group P4(3). X-ray analysis of two crystals diffracting to 1.7 and 2.0 angstroms resolution, which had slight variations in their unit-cell parameters, revealed two distinct conformations of the A-DNA helix. The two crystal structures possessed several structure and hydration features that had previously been observed in A-DNA duplexes. A comparative analysis of the present A-DNA structures and those of previously reported B-DNA crystal structures of RD-binding sites in free and protein-bound states showed the various duplexes to display several common features. Within this series, the present A-DNA duplexes adopt two conformations along the pathway from the canonical A-DNA to the B-DNA forms and the protein-bound helices display conformational features that are intermediate between those of the current A-DNA structures and that of the B-DNA-type helix of the free RD target. Based on these data and energy considerations, it is likely that the propensity of the RD-binding site to adopt the A-DNA or B-DNA conformation in solution depends on the sequence context and environmental conditions, and that the transition from either DNA form to the protein-bound conformation involves a small energy barrier.
Kitayner
Malka
M
Department of Structural Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
Rozenberg
Haim
H
Rabinovich
Dov
D
Shakked
Zippora
Z
D001483:Base Sequence; D001665:Binding Sites; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D009363:Neoplasm Proteins / Q000737:chemistry* / Q000378:metabolism; D009690:Nucleic Acid Conformation; D011487:Protein Conformation; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism
D009363:Neoplasm Proteins; D014157:Transcription Factors; D004247:DNA