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A new pattern for helix–turn–helix recognition revealed by the PU.l ETS–domain–DNA complex
Abstract
The Ets family of transcription factors, of which there are now about 35 members regulate gene expression during growth and development. They share a conserved domain of around 85 amino acids which binds as a monomer to the DNA sequence 5'-C/AGGAA/T-3'. We have determined the crystal structure of an ETS domain complexed with DNA, at 2.3-A resolution. The domain is similar to alpha + beta (winged) 'helix-turn-helix' proteins and interacts with a ten-base-pair region of duplex DNA which takes up a uniform curve of 8 degrees. The domain contacts the DNA by a novel loop-helix-loop architecture. Four of amino acids that directly interact with the DNA are highly conserved: two arginines from the recognition helix lying in the major groove, one lysine from the 'wing' that binds upstream of the core GGAA sequence, and another lysine, from the 'turn' of the 'helix-turn-helix' motif, which binds downstream and on the opposite strand.
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In the citing paper
“The crystal structure of the PU.1 DBD bound to DNA shows that the N-terminus of PU.1 faces the binding site for Pip (Kodandapani et al., 1996).”
From Assembly requirements of PU.1–Pip (IRF‐4) activator complexes: inhibiting function in vivo using fused dimers (1999) · cites this paper as Kodandapani et al., 1996
In the citing paper
“in the PU.1 DBD-DNA co-crystal structure, the N-terminus of PU.1 is adjacent to the predicted binding site of Pip.”
From Assembly requirements of PU.1–Pip (IRF‐4) activator complexes: inhibiting function in vivo using fused dimers (1999) · cites this paper as Kodandapani et al., 1996
In the citing paper
“This last suggestion is supported by the numerous protein-DNA backbone contacts observed in the PU.1-DNA co-crystal structure”
From Assembly requirements of PU.1–Pip (IRF‐4) activator complexes: inhibiting function in vivo using fused dimers (1999) · cites this paper as Kodandapani et al., 1996
In the citing paper
“In the crystal structure of PU.1-ETS domain-DNA complex, Kodandpani et al. showed that the ETS domain assumes a tight globular structure formed by three α-helices and a four-stranded anti-parallel β-sheet.”
From PU.1 and partners: regulation of haematopoietic stem cell fate in normal and malignant haematopoiesis (2009) · cites this paper as [47]
In the citing paper
“It binds to the 5′-GGAA-3′ core sequence in the major groove via the α3-recognition helix, whereas the two loops on both sides contact the phosphate backbone in the minor groove.”
From PU.1 and partners: regulation of haematopoietic stem cell fate in normal and malignant haematopoiesis (2009) · cites this paper as [47]
In the citing paper
“It has been shown in the crystal structure of PU.1 that its β3/β4 region does not interact with DNA, but is exposed to the solvent [47].”
From PU.1 and partners: regulation of haematopoietic stem cell fate in normal and malignant haematopoiesis (2009) · cites this paper as [47]
In the citing paper
“The C terminus of the PU.1 Ets-homology domain is a winged helix–turn–helix motif (8) that serves as a DNA binding domain.”
From Negative cross-talk between hematopoietic regulators: GATA proteins repress PU.1 (1999) · cites this paper as [8]
In the citing paper
“The overall structure and DNA-binding mechanism of the ETS domain is based on high-resolution molecular models of ten family members derived from both X-ray crystallography and nuclear magnetic resonance (NMR) spectroscopy (Figure 1b, Supplemental Table 2) (37–51).”
From Genomic and biochemical insights into the specificity of ETS transcription factors (2011) · cites this paper as [38]
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Targeted disruption of the PU.1 gene results in multiple hematopoietic abnormalities
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“This domain folds into a compact helix ± turn ± helix like structure with a single helix that forms base speci®c contacts in the major groove of DNA (Kodandapani et al., 1996) (Figure 3).”
Background
Metadata
- Authors
- Kodandapani, R., Pio, F., Ni, C.-Z., Piccialli, G., Klemsz, M., McKercher, S., Maki, R. A., & Ely, K. R.
- Affiliations
- Sanford Burnham Prebys Medical Discovery Institute (US)
- University of Naples Federico II (IT)
- Indiana University School of Medicine (US)
- Venue
- Nature
- Published
- 1996-04
- Volume
- 380
- Issue
- 6573
- Pages
- 456-460
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1985177466
- Cited by
- 315
- References
- 23
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 2 · 2023: 4 · 2022: 10 · 2021: 6 · 2020: 2 · 2019: 3 · 2018: 6 · 2017: 8 · 2016: 10 · 2015: 7 · 2014: 6 · 2013: 7 · 2012: 7
- FWCI
- 12.37
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Keywords
- ETS transcription factors, ETS domain, DNA-binding domain, helix-turn-helix motif, winged helix-turn-helix, DNA recognition sequence, protein-DNA complex, crystal structure, major groove, transcriptional regulation
- MeSH terms
- Amino Acid Sequence, Animals, DNA, DNA-Binding Proteins, Humans, Models, Molecular, Molecular Sequence Data, Nucleic Acid Conformation, Protein Binding, Protein Conformation, Retroviridae Proteins, Oncogenic, Sequence Homology, Amino Acid, Crystallography, X-Ray, Helix-Turn-Helix Motifs
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