New insights on DNA recognition by ets proteins from the crystal structure of the PU.1 ETS domain-DNA complex

Frédéric Pio, Ramadurgam Kodapani, Chao Zhou Ni, William Shepard, Michael Klemsz, Scott R. McKercher, Richard A. Maki, Kathryn R. Ely

Research output: Contribution to journalArticle

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Abstract

Transcription factors belonging to the ets family regulate gene expression and share a conserved ETS DNA-binding domain that binds to the core sequence 5'-(C/A)GGA(A/T)-3'. The domain is similar to α+β ('winged') helix-turn-helix DNA-binding proteins. The crystal structure of the PU.1 ETS domain complexed to a 16-base pair oligonucleotide revealed a pattern for DNA recognition from a novel loop-helix-loop architecture (Kodandapani, R., Pio, F., Ni, C.-Z., Piccialli, G., Klemsz, M., McKercher, S., Maki, R. A., and Ely, K. R. (1996) Nature 380, 456-460). Correlation of this model with mutational analyses and chemical shift data on other ets proteins confirms this complex as a paradigm for ets DNA recognition. The second helix in the helix-turn-helix motif lies deep in the major groove with specific contacts with bases in both strands in the core sequence made by conserved residues in α3. On either side of this helix, two loops contact the phosphate backbone. The DNA is bent (8°) but uniformly curved without distinct kinks. ETS domains bind DNA as a monomer yet make extensive DNA contacts over 30 Å. DNA bending likely results from phosphate neutralization of the phosphate backbone in the minor groove by both loops in the loop-helix-loop motif. Contacts from these loops stabilize DNA bending and may mediate specific base interactions by inducing a bend toward the protein.

Original languageEnglish
Pages (from-to)23329-23337
Number of pages9
JournalJournal of Biological Chemistry
Volume271
Issue number38
DOIs
StatePublished - 1996

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Crystal structure
DNA
Proteins
Phosphates
Helix-Turn-Helix Motifs
ETS Motif
Conserved Sequence
DNA-Binding Proteins
Chemical shift
Gene expression
Oligonucleotides
Base Pairing
Transcription Factors
Monomers
Gene Expression

ASJC Scopus subject areas

  • Biochemistry

Cite this

New insights on DNA recognition by ets proteins from the crystal structure of the PU.1 ETS domain-DNA complex. / Pio, Frédéric; Kodapani, Ramadurgam; Ni, Chao Zhou; Shepard, William; Klemsz, Michael; McKercher, Scott R.; Maki, Richard A.; Ely, Kathryn R.

In: Journal of Biological Chemistry, Vol. 271, No. 38, 1996, p. 23329-23337.

Research output: Contribution to journalArticle

Pio, Frédéric ; Kodapani, Ramadurgam ; Ni, Chao Zhou ; Shepard, William ; Klemsz, Michael ; McKercher, Scott R. ; Maki, Richard A. ; Ely, Kathryn R. / New insights on DNA recognition by ets proteins from the crystal structure of the PU.1 ETS domain-DNA complex. In: Journal of Biological Chemistry. 1996 ; Vol. 271, No. 38. pp. 23329-23337.
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abstract = "Transcription factors belonging to the ets family regulate gene expression and share a conserved ETS DNA-binding domain that binds to the core sequence 5'-(C/A)GGA(A/T)-3'. The domain is similar to α+β ('winged') helix-turn-helix DNA-binding proteins. The crystal structure of the PU.1 ETS domain complexed to a 16-base pair oligonucleotide revealed a pattern for DNA recognition from a novel loop-helix-loop architecture (Kodandapani, R., Pio, F., Ni, C.-Z., Piccialli, G., Klemsz, M., McKercher, S., Maki, R. A., and Ely, K. R. (1996) Nature 380, 456-460). Correlation of this model with mutational analyses and chemical shift data on other ets proteins confirms this complex as a paradigm for ets DNA recognition. The second helix in the helix-turn-helix motif lies deep in the major groove with specific contacts with bases in both strands in the core sequence made by conserved residues in α3. On either side of this helix, two loops contact the phosphate backbone. The DNA is bent (8°) but uniformly curved without distinct kinks. ETS domains bind DNA as a monomer yet make extensive DNA contacts over 30 {\AA}. DNA bending likely results from phosphate neutralization of the phosphate backbone in the minor groove by both loops in the loop-helix-loop motif. Contacts from these loops stabilize DNA bending and may mediate specific base interactions by inducing a bend toward the protein.",
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