Homeodomain complex

Hirsch, J. A. and Aggarwal, A. K. (1995). Purification, crystallization, and preliminary X-ray diffraction analysis of even-skipped homeodomain complexed to DNA. Proteins 21,268-271. 

Passner, J.M., Don Ryoo, H., Shen, L., Mann, R.S., Aggarwal, A.K. 1999. Structure of a DNA-bound Ultrabithorax-Extradenticle homeodomain complex. Nature 397, 714-719. 

Figure 9.10 Schematic diagrams illustrating the complex between DNA (orange) and one monomer of the homeodomain. The recognition helix (red) binds in the major groove of DNA and provides the sequence-specific interactions with bases in the DNA. The N-terminus (green) binds in the minor groove on the opposite side of the DNA molecule and arginine side chains make nonspecific interactions with the phosphate groups of the DNA. (Adapted from C.R. Kissinger et al Cell 63 579-590, 1990.)...

Figure 9.12 Schematic diagram of the structure of the heterodimeric yeast transcription factor Mat a2-Mat al bound to DNA. Both Mat o2 and Mat al are homeodomains containing the helix-turn-helix motif. The first helix in this motif is colored blue and the second, the recognition helix, is red. (a) The assumed structure of the Mat al homeodomain in the absence of DNA, based on Its sequence similarity to other homeodomains of known structure, (b) The structure of the Mat o2 homeodomain. The C-terminal tail (dotted) is flexible in the monomer and has no defined structure, (c) The structure of the Mat a 1-Mat a2-DNA complex. The C-terminal domain of Mat a2 (yellow) folds into an a helix (4) in the complex and interacts with the first two helices of Mat a2, to form a heterodimer that binds to DNA. (Adapted from B.J. Andrews and M.S. Donoviel, Science 270 251-253, 1995.)...

How is the binding specificity of the heterodimer achieved compared with the specificity of Mat a2 alone The crystal structure rules out the simple model that the contacts made between the Mat a2 homeodomain and DNA are altered as a result of heterodimerization. The contacts between the Mat o2 homeodomain and DNA in the heterodimer complex are virtually indistinguishable from those seen in the structure of the Mat o2 monomer bound to DNA. However, there are at least two significant factors that may account for the increased specificity of the heterodimer. First, the Mat al homeodomain makes significant contacts with the DNA, and the heterodimeric complex will therefore bind more tightly to sites that provide the contacts required by both partners. Second, site-directed mutagenesis experiments have shown that the protein-protein interactions involving the... 

Kissinger, C.R., et al. Crystal structure of an engrailed homeodomain DNA complex at 2.8 A resolution a framework for understanding homeodomain-DNA interactions. Cell 63 579-590, 1990. 

N. Using the two measured cross-correlated relaxation rates, an apparent hydrogen bond length can be determined. Data for the 15N3-1H3...15N1 hydrogen bond in A-T base pairs of Antennapedia homeodomain DNA complex with a correlation time of 20 ns has been presented. 

Li, T, Jin, Y, Vershon, A. K. and Wolberger, C. (1998). Crystal structure of the MATal/MATa2 homeodomain heterodimer in complex with DNA containing an A-tract. Nucleic Acids Res. 26, 5707-5718. 

Wolberger, C., Vershon, A. K., Liu, B., Johnson, A. D. and Pabo, C. O. (1991b). Crystal structure of a MAT a2 homeodomain-operator complex suggests a general... 

The most striking difference between DNA-binding proteins in prokaryotes and eukaryotes has to do with the symmetry of the interaction. In prokaryotes the binding proteins almost always interact in a symmetrical fashion with the DNA. In eukaryotes most of the cases that have been examined so far involve proteins that interact in an asymmetrical fashion with the DNA. In many cases the regulatory proteins interact in multisubunit complexes that contain nonidentical subunits. Four different types of structural motifs are discussed The homeodomain, the zinc finger, the leucine zipper, and the helix-loop-helix. 

These domains are often found as repeats in proteins that are involved in diverse biochemical processes. The LIM domains are thought to fimction as protein interaction modules, mediating specific contacts between members of functional complexes and modnlating the activity of some of the constituent proteins. Gronp 1 of the LIM proteins contain the LIM homeodomain (LHX), LIMK (LIM kinases) and LMO (rhombotin) subfamilies. 

Kilk, K., Magzoub, M., Pooga, M., Eriksson, L. E., Langel, U., and Graslund, A. (2001) Cellular internalization of a cargo complex with a novel peptide derived from the third helix of the islet-1 homeodomain. Comparison with the penetratin peptide. Bioconjug. Chem. 12, 911-916. 

Tucker-Kellogg L, Rould MA, Chambers KA, Ades SE, Sauer RT, Pabo CO. Engrailed (Gln50—> Lys) homeodomain-DNA complex at 1.9 A resolution structural basis for enhanced affinity and altered specificity. Structure 1997 5 1047-1054. 

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