3IGM

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

Summary for 3IGM

• Entry DOI: 10.2210/pdb3igm/pdb
• Descriptor: PF14_0633 protein, 5'-D(*TP*GP*CP*AP*TP*GP*CP*A)-3' (3 entities in total)
• Functional Keywords: ap2 domain, plasmodium falciparum, specific transcription factor, protein-dna complex, transcription-dna complex, transcription/dna
• Biological source: Plasmodium falciparum; More
• Total number of polymer chains: 6
• Total formula weight: 27336.58

Authors

Lindner, S.E.,De Silva, E.,Keck, J.L.,Llinas, M. (deposition date: 2009-07-28, release date: 2009-11-10, Last modification date: 2024-11-06)

Primary citation

Lindner, S.E.,De Silva, E.K.,Keck, J.L.,Llinas, M.
Structural Determinants of DNA Binding by a P. falciparum ApiAP2 Transcriptional Regulator.
J.Mol.Biol., 395:558-567, 2010

PubMed 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.

PubMed: 19913037
DOI: 10.1016/j.jmb.2009.11.004

Experimental method

X-RAY DIFFRACTION (2.2 Å)