title: Acquisition of a leucine zipper motif as a mechanism of antimorphy for an allele of the Drosophila Hox gene Sex combs reduced.
abstract: In 1932, Müller first used the term "antimorphic" to describe mutant alleles that have an effect that is antagonistic to that of the wild-type allele from which they were derived. In a previous characterization of mutant alleles of the Drosophila melanogaster Hox gene, Sex combs reduced (Scr), we identified the missense, antimorphic allele Scr(14), which is a Ser10-to-Leu change in the N-terminally located, bilateran-specific octapeptide motif. Here we propose that the cause of Scr(14) antimorphy is the acquisition of a leucine zipper oligomerization motif spanning the octapeptide motif and adjacently located protostome-specific LASCY motif. Analysis of the primary and predicted secondary structures of the SCR N-terminus suggests that while the SCR(+) encodes a short, α-helical region containing one putative heptad repeat, the same region in SCR(14) encodes a longer, α-helical region containing two putative heptad repeats. In addition, in vitro cross-linking assays demonstrated strong oligomerization of SCR(14) but not SCR(+). For in vivo sex comb formation, we observed reciprocal inhibition of endogenous SCR(+) and SCR(14) activity by ectopic expression of truncated SCR(14) and SCR(+) peptides, respectively. The acquisition of an oligomerization domain in SCR(14) presents a novel mechanism of antimorphy relative to the dominant negative mechanism, which maintains oligomerization between the wild-type and mutant protein subunits.
authors.affiliation: Department of Biology, The University of Western Ontario, London, Ontario 5A6 5B7, Canada lsivanan@alumni.uwo.ca.
authors.forename: Lovesha
authors.initials: L
authors.lastname: Sivanantharajah
authors.affiliation: Department of Biology, The University of Western Ontario, London, Ontario 5A6 5B7, Canada.
authors.forename: Anthony
authors.initials: A
authors.lastname: Percival-Smith
mesh_terms: D000483:Alleles; D020816:Amino Acid Motifs; D000818:Animals; D030801:Animals, Genetically Modified; D030562:Databases, Protein; D004330:Drosophila / Q000235:genetics*; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics*; D004331:Drosophila melanogaster / Q000235:genetics; D005786:Gene Expression Regulation; D005801:Genes, Homeobox; D016350:Leucine Zippers / Q000235:genetics*; D010641:Phenotype; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics*
chemical_list: D029721:Drosophila Proteins; C059627:Scr protein, Drosophila; D014157:Transcription Factors
keywords: Homeotic selector genes; Sex combs reduced; antimorph; body patterning; dominant negative; evolutionarily conserved protein motifs; interaction interface; leucine zipper