Summary information and primary citation
- PDB-id
- 3igm; DSSR-derived features in text and JSON formats
- Class
- transcription-DNA
- Method
- X-ray (2.2 Å)
- Summary
- A 2.2a crystal structure of the ap2 domain of pf14_0633 from p. falciparum, bound as a domain-swapped dimer to its cognate DNA
- Reference
- Lindner SE, De Silva EK, Keck JL, Llinas M (2010): "Structural Determinants of DNA Binding by a P. falciparum ApiAP2 Transcriptional Regulator." J.Mol.Biol., 395, 558-567. doi: 10.1016/j.jmb.2009.11.004.
- 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, at least two copies of the consensus sequence recognized by PF14_0633 are present upstream of a previously identified group of sporozoite-stage genes. Taken together, these findings illustrate how Plasmodium has adapted the AP2 DNA-binding domain for genome-wide transcriptional regulation.
