The structure of the Antennapedia homeodomain determined by NMR spectroscopy in solution: Comparison with prokaryotic repressors

Qian, Yan Qiu; Billeter, Martin; Otting, Gottfried; Müller, Martin; Gehring, Walter; Wüthrich, Kurt

doi:10.1016/0092-8674(89)90040-8

Cited by 460 publications

(257 citation statements)

References 38 publications

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“…This motif was first found in Drosophila homeotic and segmentation genes (McGinnis et al 1984;Scott & Weiner 1984) and subsequently in related genes in a wide variety of organisms including mammals, nematodes and plants (summarized by Kappen et al 1993). The homeobox encodes a homeodomain with their DNA binding activity (Muller et al 1988) which has a helix-turn-helix structure virtually identical to those observed for prokaryotic repressors (Qian et al 1989). More than one-hundred homeobox genes have so far been isolated from the mouse genome.…”

Section: Introductionmentioning

confidence: 94%

Expression of the Vax family homeobox genes suggests multiple roles in eye development

et al. 1999

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Section: Introductionmentioning

confidence: 94%

Expression of the Vax family homeobox genes suggests multiple roles in eye development

et al. 1999

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“…In spite of the low sequence homology, the secondary structure of the a2 homeo domain is remarkably similar to those of Antp and en, determined by NMR spectroscopy Qian et al 1989;Billeter et al 1990;Gehring et al 1990) and X-ray crystallography (Kissinger et al 1990), respectively. Figure 4 shows the aligned homeo domain sequences of ~2, Antp and en, with the positions of the three helices in each.…”

Section: Comparison With Antp and Enmentioning

confidence: 99%

“…Recently, the three-dimensional structures of the homeo domains from the Antp and en proteins have been determined by using nuclear magnetic resonance (NMR) spectroscopy Qian et al 1989;Billeter et al 1990;Gehring et al 19901 and X-ray crystallography (Kissinger et al 19901, respectively. The structures are very similar, with both homeo domains having three a-helices at the same positions in the aligned sequences.…”

mentioning

confidence: 99%

Secondary structure of the homeo domain of yeast alpha 2 repressor determined by NMR spectroscopy.

Phillips¹,

Vershon²,

Johnson³

et al. 1991

Genes Dev.

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The yeast a2 protein is a regulator of cell type in Saccharomyces cerevisiae. It represses transcription of a set of target genes by binding to an operator located upstream of each of these genes. The c~2 protein shares weak sequence similarity with members of the homeo domain family; the homeo domain is a 60-amino-acid segment found in many eukaryotic transcriptional regulators. In this paper we address the question of whether ~2 is structurally related to prototypical members of the homeo domain family. We used solution ~H and lSN nuclear magnetic resonance (NMR) spectroscopy to determine the secondary structure of an 83-amino-acid residue fragment of ~2 that contains the homeo domain homology. We have obtained resonance assignments for the backbone protons and nitrogens of the entire 60-residue region of the putative homeo domain and for most of the remainder of the ,Y2 fragment. The secondary structure was determined by using NOE connectivities between backbone protons, 3J~N_H. coupling constants, and dynamical information from the hydrogen exchange kinetics of the backbone amides. Three helical segments exist in the c~2 fragment consisting of residues 11-23, 32-42, and 46-60 (corresponding to residues 138-150, 159-169, and 173-187 of the intact protein). The positions of these three helices correspond extremely well to those of the Drosophila Antennapedia (Antp) and engrailed (en) homeo domains, whose three-dimensional structures have recently been determined by NMR spectroscopy and X-ray crystallography, respectively. This study reveals that in spite of low sequence similarity between the homeo domain of a2 and that of higher eukaryotes, the secondary structures of these proteins are well conserved.

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“…The N-terminal domain of the LexA repressor is considerably different in that it does not contain a canonical HTH motif. Trihelix-containing DBDs with similarities to the y6 resolvase DBD have been structurally characterized in eukaryotes and include the antennapedia homeodomain (Qian et al, 1989), the engrailed homeodomain (Kissinger et al, 1990), the homeodomain of the a 2 repressor (Wolberger et al, 1991), and repeat-3 of the c-Myb protein (Ogata et al, 1992). The POUH domain in Oct-1, Oct-2, and Pit-1 makes contacts to the DNA on the face opposite the dimeric POUS domain (Poellinger et al, 1989;Ingraham et al, 1990;Verrijzer et al, 1990;Klemm et al, 1994), as do the 2 domains of the resolvases and invertases.…”

Section: Structure-function Of the Dna Binding Domain Of Y6 Resolvasementioning

confidence: 99%

Determination of the structure of the DNA binding domain of γ^Δ resolvase in solution

1994

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The DNA binding domain (DBD) of y6 resolvase (residues 141-183) is responsible for the interaction of this sitespecific DNA recombinase with consensus site DNA within the y6 transposable element in Escherichia coli. Based on chemical-shift comparisons, the proteolytically isolated DBD displays side-chain interactions within a hydrophobic core that are highly similar to those of this domain when part of the intact enzyme (Liu T, Liu DJ, DeRose EF, Mullen GP, 1993, JBiol Chem 268:16309-16315). The structure of the DBD in solution has been determined using restraints obtained from 2-dimensional proton NMR data and is represented by 17 conformers. Experimental restraints included 458 distances based on analysis of nuclear Overhauser effect connectivities, 17 $ and x1 torsion angles based on analysis of couplings, and 17 backbone hydrogen bonds determined from NH exchange data.With respect to the computed average structure, these conformers display an RMS deviation of 0.67 A for the heavy backbone atoms and 1.49 A for all heavy atoms within residues 149-180. The DBD consists of 3 a-helices comprising residues D149-Q157, S162-T167, and R172-N183. Helix3 and helix-3 form a backbone fold, which is similar to the canonical helix-turn-helix motif. The conformation of the NH2-terminaI residues, G141-R148, appears flexible in solution. A hydrophobic core is formed by side chains donated by essentially all hydrophobic residues within the helices and turns. Helix-1 and helix-3 cross with a right-handed folding topology. The structure is consistent with a mechanism of DNA binding in which contacts are made by the hydrophilic face of helix-3 in the major groove and the amino-terminal arm in the minor groove. This structure represents an important step toward analysis of the mechanism of DNA interaction by y6 resolvase and provides initial structure-function comparisons among the divergent DBDs of related resolvases and invertases.Keywords: DNA recombinase; helix-turn-helix; NMR; recognition helix y6 Resolvase is representative of a family of DNA recombinases for which significant structural and functional information regarding site-specific DNA recombination has been obtained. However, until recently, no structural information had been available on the DNA binding domains for this protein family.The y6 resolvase protein, through formation of a multimeric complex termed a synaptosome, catalyzes the second step of y6 DNA transposition in Escherichia coli (reviewed by . In this step, a negatively supercoiled plasmid DNA containing 2 copies of the y6 transposon is converted to catenated circular DNA products, each of which contains a single copy of the transposon. The topolog-

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The structure of the Antennapedia homeodomain determined by NMR spectroscopy in solution: Comparison with prokaryotic repressors

Cited by 460 publications

References 38 publications

Expression of the Vax family homeobox genes suggests multiple roles in eye development

Expression of the Vax family homeobox genes suggests multiple roles in eye development

Secondary structure of the homeo domain of yeast alpha 2 repressor determined by NMR spectroscopy.

Determination of the structure of the DNA binding domain of γ^Δ resolvase in solution

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The structure of the Antennapedia homeodomain determined by NMR spectroscopy in solution: Comparison with prokaryotic repressors

Cited by 460 publications

References 38 publications

Expression of the Vax family homeobox genes suggests multiple roles in eye development

Expression of the Vax family homeobox genes suggests multiple roles in eye development

Secondary structure of the homeo domain of yeast alpha 2 repressor determined by NMR spectroscopy.

Determination of the structure of the DNA binding domain of γΔ resolvase in solution

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Determination of the structure of the DNA binding domain of γ^Δ resolvase in solution