Structure
Volume 7, Issue 7, 15 July 1999, Pages 841-852
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Research Article
Structure of the specificity domain of the Dorsal homologue Gambif1 bound to DNA

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Abstract

Background: NF-κB/Rel transcription factors play important roles in immunity and development in mammals and insects. Their activity is regulated by their cellular localization, homo- and heterodimerization and association with other factors on their target gene promoters. Gambif1 fromAnopheles gambiae is a member of the Rel family and a close homologue of the morphogen Dorsal, which establishes dorsoventral polarity in theDrosophila embryo.

Results: We present the crystal structure of the N-terminal specificity domain of Gambif1 bound to DNA. This first structure of an insect Rel protein–DNA complex shows that Gambif1 binds a GGG half-site element using a stack of three arginine sidechains. Differences in affinity to Dorsal binding sites in target gene promoters are predicted to arise from base changes in these GGG elements. An arginine that is conserved in class II Rel proteins (members of which contain a transcription activation domain) contacts the outermost guanines of the DNA site. This previously unseen specific contact contributes strongly to the DNA-binding affinity and might be responsible for differences in specificity between Rel proteins of class I and II.

Conclusions: The Gambif1–DNA complex structure illustrates how differences in Dorsal affinity to binding sites in developmental gene promoters are achieved. Comparison with other Rel–DNA complex structures leads to a general model for DNA recognition by Rel proteins.

Keywords

development
immune system
NF-κB
Rel protein
transcription factor

Cited by (0)

P Cramer, A Varrot and CW Müller, European Molecular Biology Laboratory, Grenoble Outstation, BP 156, F-38042 Grenoble Cedex 9, France.

C Barillas-Mury and FC Kafatos, European Molecular Biology Laboratory, Meyerhofstraße 1, D-69117 Heidelberg, Germany.

E-mail address for CW Müller (corresponding author): [email protected].

Present address for P Cramer: Department of Structural Biology, Stanford University, Stanford, CA 94305–5400, USA.

Present address for A Varrot: Chemistry Department, University of York, Heslington, York YO10 5DD, UK.

Present address for C Barillas-Mury: Department of Pathology, Colorado State University, Fort Collins, CO 80523–1671, USA.