Antennapedia

Figure 9.8 Schematic diagram of the three-dimensional structure of the Antennapedia homeodomain. The structure is built up from three a helices connected by short loops. Helices 2 and 3 form a helix-turn-hellx motif (blue and red) similar to those in procaryotic DNA-binding proteins. (Adapted from Y.Q. Qian et al.. Cell 59 573-580, 1989.)...

Figure 9.11 Amino acid sequences of homeodomains from four differenf franscription factors Anfp is from fhe Antennapedia gene in the fruitfly Drosophila, a2 is from the yeast Mat o2 gene, eng is from fhe engrailed gene in Drosophila and POU is from fhe POU homeodomain in the mammalian gene Oct-1. Residues colored green form the hydrophobic core of the homeodomain, blue form nonspecific interactions with the DNA backbone and red form contacts with the edges of the DNA bases.

The NMR study by Wiithrich and coworkers has shown that there is a cavity between the protein and the DNA in the major groove of the Antennapedia complex. There are several water molecules in this cavity with a residence time with respect to exchange with bulk water in the millisecond to nanosecond range. These observations indicate that at least some of the specific protein-DNA interactions are short-lived and mediated by water molecules. In particular, the interactions between DNA and the highly conserved Gin 50 and the invariant Asn 51 are best rationalized as a fluctuating network of weak-bonding interactions involving interfacial hydration water molecules. 

Billeter, M., et al. Determination of the nuclear magnetic resonance solution structure of an Antennapedia home-odomain DNA complex. /. Mol. Biol. 234 1084-1097, 1993. 

Frischer, L. E., Hagen, F. S., and Garber, R. L. (1986). An inversion that disrupts the Antennapedia gene causes abnormal structure and localization of RNAs. Cell 47 1017-1023. 

Gibson, G., and Gehring, W. J. (1988). Head and thoracic transformations caused by ectopic expression of Antennapedia during Drosophila development. Development 102 657-675. 

Schneuwly, S., Klemenz, R and Gehring, W. J. (1987). Redesigning the body plan of Drosophila by ectopic expression of the homeotic gene Antennapedia. Nature 325 816-818. ... 

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. 

Console S, et al. Antennapedia and HIV transactivator of transcription (TAT) protein transduction domains promote endocytosis of high molecular weight cargo upon binding to cell surface glycosaminoglycans. J Biol Chem 2003 278 35109. 

Derossi D, Calvet S, Trembleau A, et al. Cell internalization of the third helix of the antennapedia homeodomain is receptor-independent. J Biol Chem 1996 271(30) 18188-18193. 

Abbreviations. NMRI, nuclear magnetic resonance imaging Antp, antennapedia RES, reticuloendothelial system ADEPT, antibody-directed enzyme prodrug therapy TAT. 

FIGURE 28-39 Effects of mutations in homeotic genes in Drosophila, (a) Normal head, (b) Homeotic mutant (antennapedia) in which antennae are replaced by legs, (c) Normal body structure, (d) Homeotic mutant (bithorax) in which a segment has developed incorrectly to produce an extra set of wings. 

Abnormal phenotypes resulting from homeotic mutations. Antennapedia results in a pair of extra legs sprouting from the head in place of antennae. Bithorax results in an extra pair of wings appearing where halteres normally appear. 

McGinnis, W., Garber, R.L., Wirz, J., Kuriowa, A., Gehring, W.J. (1984). A conserved DNA sequence in homeotic genes of the Drosophila Antennapedia and bithorax complexes. Nature (London) 308, 428-433. 

Derossi, D., Joliot, A.H., Chassaing, G. and Prochiantz, A. (1994) The third helix of the Antennapedia homeodomain translocates through biological membranes. J. Biol. Chem., 269, 10444-10450. 

William Bateson first described in 1895. These mutations do not arrest development but transform one part of the body into another. Antennapedia mutations, for example, transform antennae into legs, which gives rise to an insect with two legs sprouting from its head, whereas bithorax mutations transform the third thorax into a second one, giving the insect an extra pair of wings. 

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