Structure of a DNA-bound Ultrabithorax–Extradenticle homeodomain complex

@article{Passner1999StructureOA,
  title={Structure of a DNA-bound Ultrabithorax–Extradenticle homeodomain complex},
  author={J. Passner and H. Ryoo and Leyi Shen and R. Mann and Aneel K. Aggarwal},
  journal={Nature},
  year={1999},
  volume={397},
  pages={714-719}
}
  • J. Passner, H. Ryoo, +2 authors Aneel K. Aggarwal
  • Published 1999
  • Biology, Medicine
  • Nature
During the development of multicellular organisms, gene expression must be tightly regulated, both spatially and temporally. One set of transcription factors that are important in animal development is encoded by the homeotic (Hox) genes, which govern the choice between alternative developmental pathways along the anterior–posterior axis. Hox proteins, such as Drosophila Ultrabithorax, have low DNA-binding specificity by themselves but gain affinity and specificity when they bind together with… Expand
Structure of the unique tetrameric STENOFOLIA homeodomain bound with DNA
TLDR
The structural and functional data reveal that STF specifically targets ‘TGA’ sequence and the cooperative tetrameric binding with DNA is key to transcriptional repression in plants, and an unprecedented HD:DNA recognition mechanism is revealed, representing the first plant HD structure from WOX family of transcription factors. Expand
Internal regulatory interactions determine DNA binding specificity by a Hox transcription factor.
TLDR
Despite a modular domain design for Hox proteins, these results suggest that multiple Hox protein regions form a network of regulatory interactions that coordinate context- and gene-specific responses. Expand
Interchange of DNA-binding modes in the deformed and ultrabithorax homeodomains: a structural role for the N-terminal arm.
TLDR
The structural details of two Dfd/Ubx chimeric HDs in complex with both the Dfd and Ubx-optimal-binding site sequences are characterized and it appears that interaction of the Ubx recognition helix with the DNA major groove is reduced and replacement of the DFD N-terminal arm does not elicit a complete interchange of the DNA-binding mode. Expand
Regulation of Hox target genes by a DNA bound Homothorax/Hox/Extradenticle complex.
TLDR
It is shown that a conserved N-terminal domain of HTH directly binds to EXD in vitro, and is sufficient to induce the nuclear localization ofEXD in vivo, however, mutating a key DNA binding residue in the HTH homeodomain abolishes many of its in vivo functions. Expand
Multiple Intrinsically Disordered Sequences Alter DNA Binding by the Homeodomain of the Drosophila Hox Protein Ultrabithorax*
TLDR
The structure of the Drosophila melanogaster Hox protein Ultrabithorax and the impact of its nonhomeodomain regions on DNA binding properties is explored and it is demonstrated that the YPWM region and the disordered microexons (termed the I1 region) inhibit DNA binding ∼2-fold, whereas the dis ordered I2 region inhibits homeodomains-DNA interaction a further ∼40-fold. Expand
Structural basis for homeodomain recognition by the cell-cycle regulator Geminin
TLDR
The solution structure of the Hox homeodomain in complex with the cell-cycle regulator, Geminin, is reported, which inhibits Hox transcriptional activity and enrolls Hox in cell proliferative control and may serve as a paradigm for interactions betweenhomeodomains and DNA-competitive peptide inhibitors. Expand
Crystal Structure of the Double Homeodomain of DUX4 in Complex with DNA.
TLDR
The crystal structure of the tandem homeodomains of DUX4 bound to DNA is reported, indicating an arginine-to-glutamate mutation, unique to primates, is responsible for the divergence in sequence recognition that likely drove coevolution of embryonically regulated repeats in primates. Expand
Dissecting the functional specificities of two Hox proteins.
TLDR
Evidence is provided that another Drosophila Hox protein, Deformed (Dfd), uses a very similar mechanism to achieve specificity in vivo, thus generalizing this mechanism and suggesting that the interaction between these DNA-binding proteins and theDNA-binding site determines the architecture of the Hox-cofactor-DNA ternary complex. Expand
Recognition of distinct target sites by a unique Labial/Extradenticle/Homothorax complex
TLDR
It is reported that the regulation of a newly identified Lab target gene does not rely on the previously established consensus Lab/Exd/Hth-binding site, but on a strongly divergent sequence, suggesting that Lab, and most probably other Hox proteins, selects different DNA sequences in regulating downstream target genes. Expand
DNA binding specificities and transcriptional activity of mirror, an Iroquois transcription factor, in Drosophila melanogaster
TLDR
To determine the DNA-binding preference of the Iroquois family members, I conducted a DNA binding site selection experiment using Drosophila Mirror and defined a novel consensus sequence ACAnnTGT, which is different from the classic HOX motif, providing evidence that this motif is the minimum requirement for Mirror binding to DNA. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 39 REFERENCES
Extradenticle protein is a selective cofactor for the Drosophila homeotics: role of the homeodomain and YPWM amino acid motif in the interaction.
TLDR
Selective interaction of the extradenticle homeodomain protein with certain Ultrabithorax and abdominal-A proteins but not with an Antennapedia protein or a more distant homeodOMain protein is demonstrated by using a yeast two-hybrid system. Expand
A structural model for a homeotic protein-extradenticle-DNA complex accounts for the choice of HOX protein in the heterodimer.
  • S. Chan, R. Mann
  • Biology, Medicine
  • Proceedings of the National Academy of Sciences of the United States of America
  • 1996
TLDR
Analysis of protein-DNA interactions that are important for forming the labial-extradenticle-DNA complex demonstrates that extradenticle prefers to bind cooperatively with different HOX proteins depending on subtle differences in the heterodimer binding site. Expand
The DNA binding specificity of ultrabithorax is modulated by cooperative interactions with extradenticle, another homeoprotein
TLDR
Cooperative interactions between Ubx protein and a divergent homeodomain protein, extradenticle (exd), that selectively increases the affinity of Ubx, but not Antp, for a particular DNA target are described. Expand
Crystal Structure of the MATa1/MATα2 Homeodomain Heterodimer Bound to DNA
The Saccharomyces cerevisiae MATa1 and MATα2 homeodomain proteins, which play a role in determining yeast cell type, form a heterodimer that binds DNA and represses transcription in a cellExpand
Extra specificity from extradenticle: the partnership between HOX and PBX/EXD homeodomain proteins.
TLDR
The unique problem posed by these highly related and developmentally important transcription factors requires additional twists to the standard solution, which are beginning to become apparent from the characterization of the HOX cofactors encoded by the extradenticle and PBX genes. Expand
Structure of the even‐skipped homeodomain complexed to AT‐rich DNA: new perspectives on homeodomain specificity.
TLDR
A crystallographic analysis of the Even‐skipped homeodomain complexed to an AT‐rich oligonucleotide at 2.0 A resolution reveals a novel arrangement of two homeodOMains bound to one 10 bp DNA sequence in a tandem fashion, which suggests a mechanism for the homeoproteins' regulatory specificity. Expand
The specificity of homeotic gene function
  • R. Mann
  • Biology, Medicine
  • BioEssays : news and reviews in molecular, cellular and developmental biology
  • 1995
TLDR
In HOM/Hox proteins, both the conserved ‘YPWM’ peptide motif and the homeodomain are important for interacting with exd, providing part of the answer as to how specificity is achieved. Expand
Crystal structure of the MATa1/MAT alpha 2 homeodomain heterodimer bound to DNA.
TLDR
The three-dimensional crystal structure of the a1/alpha 2 homeodomain heterodimer bound to DNA was determined and complex formation mediated by flexible protein-recognition peptides attached to stably folded DNA binding domains may be a general feature of the architecture of other classes of eukaryotic transcriptional regulators. Expand
An extradenticle‐induced conformational change in a HOX protein overcomes an inhibitory function of the conserved hexapeptide motif.
TLDR
It is demonstrated that a 20 bp oligonucleotide from the 5′ region of the mouse Hoxb‐1 gene is sufficient to direct an expression pattern in Drosophila that is very similar to endogenous lab, consistent with a mechanism whereby the LAB hexapeptide inhibits LAB function by inhibiting DNA binding and that an EXD‐induced conformational change in LAB relieves this inhibition, promoting highly specific interactions with biologically relevant binding sites. Expand
Comparison of X-ray and NMR structures for the Antennapedia homeodomain–DNA complex
TLDR
The synthesis of X-ray and NMR studies provides a unified, general model for homeodomain–DNA interactions and reveals a well-defined set of contacts and also reveals the locations and roles of water molecules at the protein–DNA interface. Expand
...
1
2
3
4
...