3q2b

Crystal Structure of an Actin Depolymerizing Factor

spinqualitylabelsall models 3q2b, resolution 1.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3q2b is a 1 chain structure with sequence from Plafx. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: BME, TAR Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [CADF1_PLAFX] Not involved in actin polymerisation, instead functions to stimulate nucleotide exchange on monomeric actin and influence turnover of the small amount of cytosolic actin microfilaments. Essential for erythrocytic schizogony. Publication Abstract from PubMed Malaria parasite cell motility is a process that is dependent on the dynamic turnover of parasite-derived actin filaments. Despite its central role, actin's polymerization state is controlled by a set of identifiable regulators that is markedly reduced compared with those of other eukaryotic cells. In Plasmodium falciparum, the most virulent species that affects humans, this minimal repertoire includes two members of the actin-depolymerizing factor/cofilin (AC) family of proteins, P. falciparum actin-depolymerizing factor 1 (PfADF1) and P. falciparum actin-depolymerizing factor 2. This essential class of actin regulator is involved in the control of filament dynamics at multiple levels, from monomer binding through to filament depolymerization and severing. Previous biochemical analyses have suggested that PfADF1 sequesters monomeric actin but, unlike most eukaryotic counterparts, has limited potential to bind or depolymerize filaments. The molecular basis for these unusual properties and implications for parasite cell motility have not been established. Here we present the crystal structure of an apicomplexan AC protein, PfADF1. We show that PfADF1 lacks critical residues previously implicated as essential for AC-mediated actin filament binding and disassembly, having a substantially reduced filament-binding loop and C-terminal alpha4 helix. Despite this divergence in structure, we demonstrate that PfADF1 is capable of efficient actin filament severing. Furthermore, this severing occurs despite PfADF1's low binding affinity for filaments. Comparative structural analysis along with biochemical and microscopy evidence establishes that severing is reliant on the availability of an exposed basic residue in the filament-binding loop, a conserved minimal requirement that defines AC-mediated filament disassembly across eukaryotic cells. Minimal requirements for actin filament disassembly revealed by structural analysis of malaria parasite actin-depolymerizing factor 1.,Wong W, Skau CT, Marapana DS, Hanssen E, Taylor NL, Riglar DT, Zuccala ES, Angrisano F, Lewis H, Catimel B, Clarke OB, Kershaw NJ, Perugini MA, Kovar DR, Gulbis JM, Baum J Proc Natl Acad Sci U S A. 2011 Jun 14;108(24):9869-74. Epub 2011 May 31. PMID:21628589 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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