Structural determinants of DNA binding by a P. falciparum ApiAP2 transcriptional regulator.

Journal of Molecular Biology
Scott E LindnerManuel Llinás

Abstract

Putative transcription factors have only recently been identified in the Plasmodium spp., with the major family of regulators comprising the Apicomplexan Apetala2 (AP2) proteins. To better understand the DNA-binding mechanisms of these transcriptional regulators, we characterized the structure and in vitro function of an AP2 DNA-binding domain from a prototypical Apicomplexan AP2 protein, PF14_0633 from Plasmodium falciparum. The X-ray crystal structure of the PF14_0633 AP2 domain bound to DNA reveals a beta-sheet fold that binds the DNA major groove through base-specific and backbone contacts; a prominent alpha-helix supports the beta-sheet structure. Substitution of predicted DNA-binding residues with alanine weakened or eliminated DNA binding in solution. In contrast to plant AP2 domains, the PF14_0633 AP2 domain dimerizes upon binding to DNA through a domain-swapping mechanism in which the alpha-helices of the AP2 domains pack against the beta-sheets of the dimer mates. DNA-induced dimerization of PF14_0633 may be important for tethering two distal DNA loci together in the nucleus and/or for inducing functional rearrangements of its domains to facilitate transcriptional regulation. Consistent with a multisite binding mode, ...Continue Reading

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Citations

Dec 2, 2011·Journal of Biomedicine & Biotechnology·Renu TutejaVirander Singh Chauhan
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