A single amino acid can determine the DNA binding specificity of homeodomain proteins

Jessica Trelsman, Pierre Gönczy, Malini Vashishtha, Esther Harris, Claude Desplan

Research output: Contribution to journalArticle

Abstract

Many Drosophila developmental genes contain a DNA binding domain encoded by the homeobox. This homeodomain contains a region distantly homologous to the helix-turn-helix motif present in several prokaryotic DNA binding proteins. We investigated the nature of homeodomain-DNA interactions by making a series of mutations in the helix-turn-helix motif of the Drosophlia homeodomain protein Paired (Prd). This protein does not recognize sequences bound by the homeodomain proteins Fushi tarazu (Ftz) or Bicoid (Bcd). We show that changing a single amino acid at the C-terminus of the recognition helix is both necessary and sufficient to confer the DNA binding specificity of either Ftz or Bcd on Prd. This simple rule indicates that the amino acids that determine the specificity of homeodomains are different from those mediating protein-DNA contacts in prokaryotic proteins. We further show that Prd contains two DNA binding activities. The Prd homeodomain is responsible for one of them while the other is not dependent on the recognition helix.

Original languageEnglish (US)
Pages (from-to)553-562
Number of pages10
JournalCell
Volume59
Issue number3
DOIs
StatePublished - Nov 3 1989

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Homeodomain Proteins
Amino Acids
Helix-Turn-Helix Motifs
DNA
Developmental Genes
Proteins
Homeobox Genes
DNA-Binding Proteins
Drosophila
Genes
Mutation

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

A single amino acid can determine the DNA binding specificity of homeodomain proteins. / Trelsman, Jessica; Gönczy, Pierre; Vashishtha, Malini; Harris, Esther; Desplan, Claude.

In: Cell, Vol. 59, No. 3, 03.11.1989, p. 553-562.

Research output: Contribution to journalArticle

Trelsman, Jessica ; Gönczy, Pierre ; Vashishtha, Malini ; Harris, Esther ; Desplan, Claude. / A single amino acid can determine the DNA binding specificity of homeodomain proteins. In: Cell. 1989 ; Vol. 59, No. 3. pp. 553-562.
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